Nancy Walsh

Early childhood colonization with the major human commensal microbe Helicobacter pylori may be protective against asthma, according to a recent study.

According to the “hygiene hypothesis,” the rise in asthma and allergic disorders that occurred during the 20th century relates to a reduction in exposure to environmental antigens and alterations in gut microbiota during development of the immune system.

Changes in human colonization with H. pylori represent a “biologically plausible” candidate in the hygiene hypothesis, asserted Dr. Yu Chen of New York University and Dr. Martin J. Blaser of New York University and the Veterans Affairs Medical Center, New York.

The investigators explained that there has been a near universal association of this organism and humans for at least 58,000 years, since the time of the initial human migration out of Africa. Seropositivity is generally acquired during the first few years of life and remains lifelong unless eradicated by antibiotics.

The prevalence of seropositivity began to decline early in the last century, a trend that was paralleled by an increase in asthma. Today the seroprevalence in native-born children younger than 10 years in the United States stands at less than 10%, according to the investigators (J. Infect. Dis. 2008;198:553-60).

In order to investigate whether this decline in H. pylori colonization could be linked to the increase in asthma in children, the New York investigators analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999-2000, which is a representative sample of the U.S. population.

They estimated odds ratios for asthma, wheezing, and other allergic conditions such as allergic rhinitis and eczema, with adjustment for age, body mass index, smoking, education level, race, country of origin, and also for antibiotic and corticosteroid use in the previous month, medical insurance status, and household income.

The sample included 7,412 participants, 3,327 of whom were younger than 20 years. Overall seroprevalence for H. pylori was 26%, but prevalence was lower in younger groups, with only 5% of children younger than 10 years being seropositive.

For the entire cohort there was a trend toward an inverse association between seropositivity for H. pylori and ever having had asthma and for having had one or more asthma attacks during the past year. There was a significant inverse association between H. pylori seropositivity and having had eczema or dermatitis in the past year, with an odds ratio of 0.73.

Among the 3,327 subjects who were age 19 years or younger at the time of data collection, there was a strong inverse association between H. pylori positivity and onset of asthma before 5 years of age, with an odds ratio of 0.58.

Furthermore, among those aged 3-13 years, strong inverse associations were seen for seropositivity and current asthma, ever having had asthma, and having had allergic rhinitis during the previous year.

A possible explanation for the recent decline in H. pylori colonization is the widespread use of antibiotics in children for conditions such as otitis media, according to Dr. Chen and Dr. Blaser.

In fact, they noted, their study population was “strongly impacted” by antibiotics, with 11% of those younger than 10 years having had an antibiotic during the month before data collection. Eradication rates of H. pylori with antibiotic monotherapy range from 10% to 50%.

Among the characteristics that favor H. pylori as protective is its “intimate relationship with the gastric mucosa, where it injects bacterial constituents into epithelial cells,” Dr. Chen and Dr. Blaser wrote.

In seropositive subjects, lymphoid cells such as helper and regulatory T cells are found in the gastric lamina propria. These are absent in seronegative persons.

There was a strong inverse association between H. pylori positivity and onset of asthma before age 5. DR. BLASER

Early childhood colonization with the major human commensal microbe Helicobacter pylori may be protective against asthma, according to a recent study.

According to the “hygiene hypothesis,” the rise in asthma and allergic disorders that occurred during the 20th century relates to a reduction in exposure to environmental antigens and alterations in gut microbiota during development of the immune system.

Changes in human colonization with H. pylori represent a “biologically plausible” candidate in the hygiene hypothesis, asserted Dr. Yu Chen of New York University and Dr. Martin J. Blaser of New York University and the Veterans Affairs Medical Center, New York.

The investigators explained that there has been a near universal association of this organism and humans for at least 58,000 years, since the time of the initial human migration out of Africa. Seropositivity is generally acquired during the first few years of life and remains lifelong unless eradicated by antibiotics.

The prevalence of seropositivity began to decline early in the last century, a trend that was paralleled by an increase in asthma. Today the seroprevalence in native-born children younger than 10 years in the United States stands at less than 10%, according to the investigators (J. Infect. Dis. 2008;198:553-60).

In order to investigate whether this decline in H. pylori colonization could be linked to the increase in asthma in children, the New York investigators analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999-2000, which is a representative sample of the U.S. population.

They estimated odds ratios for asthma, wheezing, and other allergic conditions such as allergic rhinitis and eczema, with adjustment for age, body mass index, smoking, education level, race, country of origin, and also for antibiotic and corticosteroid use in the previous month, medical insurance status, and household income.

The sample included 7,412 participants, 3,327 of whom were younger than 20 years. Overall seroprevalence for H. pylori was 26%, but prevalence was lower in younger groups, with only 5% of children younger than 10 years being seropositive.

For the entire cohort there was a trend toward an inverse association between seropositivity for H. pylori and ever having had asthma and for having had one or more asthma attacks during the past year. There was a significant inverse association between H. pylori seropositivity and having had eczema or dermatitis in the past year, with an odds ratio of 0.73.

Among the 3,327 subjects who were age 19 years or younger at the time of data collection, there was a strong inverse association between H. pylori positivity and onset of asthma before 5 years of age, with an odds ratio of 0.58.

Furthermore, among those aged 3-13 years, strong inverse associations were seen for seropositivity and current asthma, ever having had asthma, and having had allergic rhinitis during the previous year.

A possible explanation for the recent decline in H. pylori colonization is the widespread use of antibiotics in children for conditions such as otitis media, according to Dr. Chen and Dr. Blaser.

In fact, they noted, their study population was “strongly impacted” by antibiotics, with 11% of those younger than 10 years having had an antibiotic during the month before data collection. Eradication rates of H. pylori with antibiotic monotherapy range from 10% to 50%.

Among the characteristics that favor H. pylori as protective is its “intimate relationship with the gastric mucosa, where it injects bacterial constituents into epithelial cells,” Dr. Chen and Dr. Blaser wrote.

In seropositive subjects, lymphoid cells such as helper and regulatory T cells are found in the gastric lamina propria. These are absent in seronegative persons.

There was a strong inverse association between H. pylori positivity and onset of asthma before age 5. DR. BLASER

Early childhood colonization with the major human commensal microbe Helicobacter pylori may be protective against asthma, according to a recent study.

According to the “hygiene hypothesis,” the rise in asthma and allergic disorders that occurred during the 20th century relates to a reduction in exposure to environmental antigens and alterations in gut microbiota during development of the immune system.

Changes in human colonization with H. pylori represent a “biologically plausible” candidate in the hygiene hypothesis, asserted Dr. Yu Chen of New York University and Dr. Martin J. Blaser of New York University and the Veterans Affairs Medical Center, New York.

The investigators explained that there has been a near universal association of this organism and humans for at least 58,000 years, since the time of the initial human migration out of Africa. Seropositivity is generally acquired during the first few years of life and remains lifelong unless eradicated by antibiotics.

The prevalence of seropositivity began to decline early in the last century, a trend that was paralleled by an increase in asthma. Today the seroprevalence in native-born children younger than 10 years in the United States stands at less than 10%, according to the investigators (J. Infect. Dis. 2008;198:553-60).

In order to investigate whether this decline in H. pylori colonization could be linked to the increase in asthma in children, the New York investigators analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999-2000, which is a representative sample of the U.S. population.

They estimated odds ratios for asthma, wheezing, and other allergic conditions such as allergic rhinitis and eczema, with adjustment for age, body mass index, smoking, education level, race, country of origin, and also for antibiotic and corticosteroid use in the previous month, medical insurance status, and household income.

The sample included 7,412 participants, 3,327 of whom were younger than 20 years. Overall seroprevalence for H. pylori was 26%, but prevalence was lower in younger groups, with only 5% of children younger than 10 years being seropositive.

For the entire cohort there was a trend toward an inverse association between seropositivity for H. pylori and ever having had asthma and for having had one or more asthma attacks during the past year. There was a significant inverse association between H. pylori seropositivity and having had eczema or dermatitis in the past year, with an odds ratio of 0.73.

Among the 3,327 subjects who were age 19 years or younger at the time of data collection, there was a strong inverse association between H. pylori positivity and onset of asthma before 5 years of age, with an odds ratio of 0.58.

Furthermore, among those aged 3-13 years, strong inverse associations were seen for seropositivity and current asthma, ever having had asthma, and having had allergic rhinitis during the previous year.

A possible explanation for the recent decline in H. pylori colonization is the widespread use of antibiotics in children for conditions such as otitis media, according to Dr. Chen and Dr. Blaser.

In fact, they noted, their study population was “strongly impacted” by antibiotics, with 11% of those younger than 10 years having had an antibiotic during the month before data collection. Eradication rates of H. pylori with antibiotic monotherapy range from 10% to 50%.

Among the characteristics that favor H. pylori as protective is its “intimate relationship with the gastric mucosa, where it injects bacterial constituents into epithelial cells,” Dr. Chen and Dr. Blaser wrote.

In seropositive subjects, lymphoid cells such as helper and regulatory T cells are found in the gastric lamina propria. These are absent in seronegative persons.

There was a strong inverse association between H. pylori positivity and onset of asthma before age 5. DR. BLASER

PARIS — Heavy coffee drinking was associated with progression of undifferentiated arthritis to rheumatoid arthritis in an analysis of data from a Norwegian early arthritis clinic.

The study included 280 patients aged 18–75 years with arthritis of at least one joint. The mean age was 45.7 years, median disease duration was 23 days, and 55% were women, Dr. Maria D. Mjaavatten said at the annual European Congress of Rheumatology.

Data were collected from a structured patient history. Examinations included swollen and tender joint counts, measurement of C-reactive protein and erythrocyte sedimentation rate, and patient-reported health status.

At baseline, 130 patients had monoarthritis, 96 had oligoarthritis, and 54 had polyarthritis. At 1 year, 30 of these patients (10.7%) had developed rheumatoid arthritis (RA). Multivariate analysis showed the strongest predictor of RA development was a positive titer of anti-cyclic citrullinated peptide (CCP) at presentation, with an odds ratio of 73.23.

But drinking 10 or more cups of coffee daily also was associated with an elevated risk (OR, 22.50), Dr. Mjaavatten of the department of rheumatology, Diakonhjemmet Hospital, Oslo, wrote in a poster.

The link of coffee intake with RA also was seen in earlier studies. In the Mini-Finland Health Survey, carried out between 1978 and 1980, the odds ratio for RA was 14.80 in those with a daily coffee intake of 11 or more cups. After adjustment for confounders including age, sex, smoking, alcohol intake, body mass index, and serum cholesterol, the relative risk was 2.20 for those drinking four or more cups of coffee daily (Ann. Rheum. Dis. 2000;59:631–5).

A study from Iowa implicated decaffeinated coffee. Researchers reported that subjects who drank four or more cups a day had a relative risk of 2.58 for RA, suggesting that exposure to the solvents used for extracting caffeine before the mid-1970s might have played a role (Arthritis Rheum. 2002;46:83–91).

A case-control study in Denmark between 2002 and 2004 found that subjects who were shared epitope carriers and smoked, drank more than five cups of coffee each day, or used oral contraceptives were at high risk for anti-CCP-positive RA.

The researchers cited the hypothesis that exposure to environmental stimuli might be a primary triggering event for RA, with tobacco smoke being the prototype because it induces the presentation of citrullinated autoantigens in the lungs in genetically predisposed persons, which activates the adaptive immune response. They suggested coffee also might operate in this citrullination process, contributing to anti-CCP-positive RA (Arthritis Rheum. 2007;56:1446–53).

Further investigation of coffee intake in RA development is needed, Dr. Mjaavatten said, noting her results should be interpreted with caution, because the RAincidence was low in this cohort.

PARIS — Heavy coffee drinking was associated with progression of undifferentiated arthritis to rheumatoid arthritis in an analysis of data from a Norwegian early arthritis clinic.

The study included 280 patients aged 18–75 years with arthritis of at least one joint. The mean age was 45.7 years, median disease duration was 23 days, and 55% were women, Dr. Maria D. Mjaavatten said at the annual European Congress of Rheumatology.

Data were collected from a structured patient history. Examinations included swollen and tender joint counts, measurement of C-reactive protein and erythrocyte sedimentation rate, and patient-reported health status.

At baseline, 130 patients had monoarthritis, 96 had oligoarthritis, and 54 had polyarthritis. At 1 year, 30 of these patients (10.7%) had developed rheumatoid arthritis (RA). Multivariate analysis showed the strongest predictor of RA development was a positive titer of anti-cyclic citrullinated peptide (CCP) at presentation, with an odds ratio of 73.23.

But drinking 10 or more cups of coffee daily also was associated with an elevated risk (OR, 22.50), Dr. Mjaavatten of the department of rheumatology, Diakonhjemmet Hospital, Oslo, wrote in a poster.

The link of coffee intake with RA also was seen in earlier studies. In the Mini-Finland Health Survey, carried out between 1978 and 1980, the odds ratio for RA was 14.80 in those with a daily coffee intake of 11 or more cups. After adjustment for confounders including age, sex, smoking, alcohol intake, body mass index, and serum cholesterol, the relative risk was 2.20 for those drinking four or more cups of coffee daily (Ann. Rheum. Dis. 2000;59:631–5).

A study from Iowa implicated decaffeinated coffee. Researchers reported that subjects who drank four or more cups a day had a relative risk of 2.58 for RA, suggesting that exposure to the solvents used for extracting caffeine before the mid-1970s might have played a role (Arthritis Rheum. 2002;46:83–91).

A case-control study in Denmark between 2002 and 2004 found that subjects who were shared epitope carriers and smoked, drank more than five cups of coffee each day, or used oral contraceptives were at high risk for anti-CCP-positive RA.

The researchers cited the hypothesis that exposure to environmental stimuli might be a primary triggering event for RA, with tobacco smoke being the prototype because it induces the presentation of citrullinated autoantigens in the lungs in genetically predisposed persons, which activates the adaptive immune response. They suggested coffee also might operate in this citrullination process, contributing to anti-CCP-positive RA (Arthritis Rheum. 2007;56:1446–53).

Further investigation of coffee intake in RA development is needed, Dr. Mjaavatten said, noting her results should be interpreted with caution, because the RAincidence was low in this cohort.

PARIS — Heavy coffee drinking was associated with progression of undifferentiated arthritis to rheumatoid arthritis in an analysis of data from a Norwegian early arthritis clinic.

The study included 280 patients aged 18–75 years with arthritis of at least one joint. The mean age was 45.7 years, median disease duration was 23 days, and 55% were women, Dr. Maria D. Mjaavatten said at the annual European Congress of Rheumatology.

Data were collected from a structured patient history. Examinations included swollen and tender joint counts, measurement of C-reactive protein and erythrocyte sedimentation rate, and patient-reported health status.

At baseline, 130 patients had monoarthritis, 96 had oligoarthritis, and 54 had polyarthritis. At 1 year, 30 of these patients (10.7%) had developed rheumatoid arthritis (RA). Multivariate analysis showed the strongest predictor of RA development was a positive titer of anti-cyclic citrullinated peptide (CCP) at presentation, with an odds ratio of 73.23.

But drinking 10 or more cups of coffee daily also was associated with an elevated risk (OR, 22.50), Dr. Mjaavatten of the department of rheumatology, Diakonhjemmet Hospital, Oslo, wrote in a poster.

The link of coffee intake with RA also was seen in earlier studies. In the Mini-Finland Health Survey, carried out between 1978 and 1980, the odds ratio for RA was 14.80 in those with a daily coffee intake of 11 or more cups. After adjustment for confounders including age, sex, smoking, alcohol intake, body mass index, and serum cholesterol, the relative risk was 2.20 for those drinking four or more cups of coffee daily (Ann. Rheum. Dis. 2000;59:631–5).

A study from Iowa implicated decaffeinated coffee. Researchers reported that subjects who drank four or more cups a day had a relative risk of 2.58 for RA, suggesting that exposure to the solvents used for extracting caffeine before the mid-1970s might have played a role (Arthritis Rheum. 2002;46:83–91).

A case-control study in Denmark between 2002 and 2004 found that subjects who were shared epitope carriers and smoked, drank more than five cups of coffee each day, or used oral contraceptives were at high risk for anti-CCP-positive RA.

The researchers cited the hypothesis that exposure to environmental stimuli might be a primary triggering event for RA, with tobacco smoke being the prototype because it induces the presentation of citrullinated autoantigens in the lungs in genetically predisposed persons, which activates the adaptive immune response. They suggested coffee also might operate in this citrullination process, contributing to anti-CCP-positive RA (Arthritis Rheum. 2007;56:1446–53).

Further investigation of coffee intake in RA development is needed, Dr. Mjaavatten said, noting her results should be interpreted with caution, because the RAincidence was low in this cohort.

PARIS — Methicillin-resistant Staphylococcus aureus infections have been reported for the first time in patients with rheumatoid arthritis being treated with tumor necrosis factor inhibitors.

In a poster presented at the annual European Congress of Rheumatology, Dr. Jack Lichtenstein noted that he had observed that several of his patients receiving tumor necrosis factor (TNF) inhibitors developed severe methicillin-resistant S. aureus (MRSA) infections, so he undertook a review of medical records of all patients in his clinical practice being treated with these drugs between August 2003 and July 2006 to determine the overall incidence and severity of these infections.

Among 430 patients receiving infliximab, etanercept, or adalimumab, 15 developed MRSA infections, had to stop TNF inhibitor therapy and received intravenous antibiotics, reported Dr. Lichtenstein, a rheumatologist in group practice in Annapolis, Md.

In addition, 12 patients required hospitalization.

Concomitant immunosuppressive treatment included prednisone in 12 patients and methotrexate in 6. Clinical presentations included cellulitis in six, osteomyelitis in three, sinusitis in two, and septic arthritis, mastitis, pneumonia, and Fournier's gangrene with sepsis in one each.

More than half of the infections occurred within the first 6 months of treatment, but four developed after more than a year of therapy. Six were seen in patients on infliximab, five in those on etanercept, and four in those on adalimumab.

Another 10 patients developed methicillin-sensitive S. aureus (MSSA) infections, 5 of which were cellulitis, 4 of which were septic arthritis, and 1 osteomyelitis. Seven of these required hospitalization and nine were given intravenous antibiotics.

Other bacterial infections seen in anti-TNF-treated patients included gram-negative bacterial cellulitis in four, severe Clostridium difficile infections in three, and tuberculosis with fatal pneumonia, Mycobacterium marinum joint infection, and Nocardia pneumonia in one each.

Other infections for which no bacterial agent was cultured included cellulitis in nine, pneumonia in six, and diverticulitis in two.

MRSA and MSSA infections were more common than were other bacterial infections in this group of anti-TNF-treated patients, according to Dr. Lichtenstein, who noted that MRSA infections may have a protracted course and may not respond to available treatments.

Attempts to restart TNF inhibitors after control of the MRSA infections led to recurrent infection in seven patients, and only two patients were able to resume TNF inhibitor therapy after the infection was controlled.

Dr. Lichtenstein wrote that he would no longer continue the use of TNF inhibitors in patients with MRSA or MSSA infections.

About one-third of Americans are carriers of MSSA and 0.8% carry MRSA, and infections with these organisms are expected to be common in immunocompromised patients such as these.

This study was wholly funded by the investigators and had no pharmaceutical, institutional, or financial support.

PARIS — Methicillin-resistant Staphylococcus aureus infections have been reported for the first time in patients with rheumatoid arthritis being treated with tumor necrosis factor inhibitors.

In a poster presented at the annual European Congress of Rheumatology, Dr. Jack Lichtenstein noted that he had observed that several of his patients receiving tumor necrosis factor (TNF) inhibitors developed severe methicillin-resistant S. aureus (MRSA) infections, so he undertook a review of medical records of all patients in his clinical practice being treated with these drugs between August 2003 and July 2006 to determine the overall incidence and severity of these infections.

Among 430 patients receiving infliximab, etanercept, or adalimumab, 15 developed MRSA infections, had to stop TNF inhibitor therapy and received intravenous antibiotics, reported Dr. Lichtenstein, a rheumatologist in group practice in Annapolis, Md.

In addition, 12 patients required hospitalization.

Concomitant immunosuppressive treatment included prednisone in 12 patients and methotrexate in 6. Clinical presentations included cellulitis in six, osteomyelitis in three, sinusitis in two, and septic arthritis, mastitis, pneumonia, and Fournier's gangrene with sepsis in one each.

More than half of the infections occurred within the first 6 months of treatment, but four developed after more than a year of therapy. Six were seen in patients on infliximab, five in those on etanercept, and four in those on adalimumab.

Another 10 patients developed methicillin-sensitive S. aureus (MSSA) infections, 5 of which were cellulitis, 4 of which were septic arthritis, and 1 osteomyelitis. Seven of these required hospitalization and nine were given intravenous antibiotics.

Other bacterial infections seen in anti-TNF-treated patients included gram-negative bacterial cellulitis in four, severe Clostridium difficile infections in three, and tuberculosis with fatal pneumonia, Mycobacterium marinum joint infection, and Nocardia pneumonia in one each.

Other infections for which no bacterial agent was cultured included cellulitis in nine, pneumonia in six, and diverticulitis in two.

MRSA and MSSA infections were more common than were other bacterial infections in this group of anti-TNF-treated patients, according to Dr. Lichtenstein, who noted that MRSA infections may have a protracted course and may not respond to available treatments.

Attempts to restart TNF inhibitors after control of the MRSA infections led to recurrent infection in seven patients, and only two patients were able to resume TNF inhibitor therapy after the infection was controlled.

Dr. Lichtenstein wrote that he would no longer continue the use of TNF inhibitors in patients with MRSA or MSSA infections.

About one-third of Americans are carriers of MSSA and 0.8% carry MRSA, and infections with these organisms are expected to be common in immunocompromised patients such as these.

This study was wholly funded by the investigators and had no pharmaceutical, institutional, or financial support.

PARIS — Methicillin-resistant Staphylococcus aureus infections have been reported for the first time in patients with rheumatoid arthritis being treated with tumor necrosis factor inhibitors.

In a poster presented at the annual European Congress of Rheumatology, Dr. Jack Lichtenstein noted that he had observed that several of his patients receiving tumor necrosis factor (TNF) inhibitors developed severe methicillin-resistant S. aureus (MRSA) infections, so he undertook a review of medical records of all patients in his clinical practice being treated with these drugs between August 2003 and July 2006 to determine the overall incidence and severity of these infections.

Among 430 patients receiving infliximab, etanercept, or adalimumab, 15 developed MRSA infections, had to stop TNF inhibitor therapy and received intravenous antibiotics, reported Dr. Lichtenstein, a rheumatologist in group practice in Annapolis, Md.

In addition, 12 patients required hospitalization.

Concomitant immunosuppressive treatment included prednisone in 12 patients and methotrexate in 6. Clinical presentations included cellulitis in six, osteomyelitis in three, sinusitis in two, and septic arthritis, mastitis, pneumonia, and Fournier's gangrene with sepsis in one each.

More than half of the infections occurred within the first 6 months of treatment, but four developed after more than a year of therapy. Six were seen in patients on infliximab, five in those on etanercept, and four in those on adalimumab.

Another 10 patients developed methicillin-sensitive S. aureus (MSSA) infections, 5 of which were cellulitis, 4 of which were septic arthritis, and 1 osteomyelitis. Seven of these required hospitalization and nine were given intravenous antibiotics.

Other bacterial infections seen in anti-TNF-treated patients included gram-negative bacterial cellulitis in four, severe Clostridium difficile infections in three, and tuberculosis with fatal pneumonia, Mycobacterium marinum joint infection, and Nocardia pneumonia in one each.

Other infections for which no bacterial agent was cultured included cellulitis in nine, pneumonia in six, and diverticulitis in two.

MRSA and MSSA infections were more common than were other bacterial infections in this group of anti-TNF-treated patients, according to Dr. Lichtenstein, who noted that MRSA infections may have a protracted course and may not respond to available treatments.

Attempts to restart TNF inhibitors after control of the MRSA infections led to recurrent infection in seven patients, and only two patients were able to resume TNF inhibitor therapy after the infection was controlled.

Dr. Lichtenstein wrote that he would no longer continue the use of TNF inhibitors in patients with MRSA or MSSA infections.

About one-third of Americans are carriers of MSSA and 0.8% carry MRSA, and infections with these organisms are expected to be common in immunocompromised patients such as these.

This study was wholly funded by the investigators and had no pharmaceutical, institutional, or financial support.

TORONTO — Lung function abnormalities are present at age 8 years in children with sickle cell disease, and the subsequent rate of decline is between 2% and 3% a year, according to new data.

“We were aware [of the lung function abnormalities] from cross-sectional studies, but they only look at one time point,” and not across childhood,” Dr. Joanna MacLean told an international conference of the American Thoracic Society.

The pattern of change, whether obstructive or restrictive, in pulmonary function also has not been well delineated in sickle cell disease. The researchers sought clarity because “there is a high mortality in early adulthood in sickle cell disease, with a major contributor being respiratory disease,” said Dr. MacLean of the Hospital for Sick Children, Toronto.

The hospital's sickle cell clinic began requiring pulmonary function testing in 1989. Data for an unselected cohort of 413 children from then until 2005, beginning at age 8 years, were collected and analyzed using linear mixed effects modeling and compared with data for race-matched predicted values and reference equations in the African American population from the third National Health and Nutrition Examination Survey (NHANES III).

The study examined the contributions of age, gender, serum hemoglobin levels, and β-globin genotype on longitudinal changes in spirometry and lung volumes.

The sample consisted of 1,357 pulmonary function test results and 1,129 total lung capacity measurements. About 46% of the records were for males, and the records were evenly distributed across age groups, with a mean age of 12.7 years.

Significant declines were seen in percent predicted values for forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), though not for the FEV1/FVC ratio. Total lung capacity (TLC) and residual volume/TLC ratios demonstrated a similar pattern of change.

There has been considerable interest in the relationship between sickle cell disease and asthma, but the spirometry data suggest a restrictive, rather than an obstructive, pattern. “It is possible that early in childhood, the pattern is more obstructive, as in asthma; but [toward] adulthood, the changes become fixed, showing a more restrictive pattern,” she said in a press conference.

Previous data suggested early adulthood mortality is worse in females, but the current results suggested boys and girls alike had a decline in FEV1 of 2.9% predicted per year.

The role of sickle cell genotype, hemoglobin SS or SC, was also evaluated. The SS genotype is more common and considered worse, but has never been examined in terms of lung function. “Children with the hemoglobin SS genotype had a rate of decline in lung function that was twice that of those with the SC genotype,” she said. This novel finding is to be investigated.

TORONTO — Lung function abnormalities are present at age 8 years in children with sickle cell disease, and the subsequent rate of decline is between 2% and 3% a year, according to new data.

“We were aware [of the lung function abnormalities] from cross-sectional studies, but they only look at one time point,” and not across childhood,” Dr. Joanna MacLean told an international conference of the American Thoracic Society.

The pattern of change, whether obstructive or restrictive, in pulmonary function also has not been well delineated in sickle cell disease. The researchers sought clarity because “there is a high mortality in early adulthood in sickle cell disease, with a major contributor being respiratory disease,” said Dr. MacLean of the Hospital for Sick Children, Toronto.

The hospital's sickle cell clinic began requiring pulmonary function testing in 1989. Data for an unselected cohort of 413 children from then until 2005, beginning at age 8 years, were collected and analyzed using linear mixed effects modeling and compared with data for race-matched predicted values and reference equations in the African American population from the third National Health and Nutrition Examination Survey (NHANES III).

The study examined the contributions of age, gender, serum hemoglobin levels, and β-globin genotype on longitudinal changes in spirometry and lung volumes.

The sample consisted of 1,357 pulmonary function test results and 1,129 total lung capacity measurements. About 46% of the records were for males, and the records were evenly distributed across age groups, with a mean age of 12.7 years.

Significant declines were seen in percent predicted values for forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), though not for the FEV1/FVC ratio. Total lung capacity (TLC) and residual volume/TLC ratios demonstrated a similar pattern of change.

There has been considerable interest in the relationship between sickle cell disease and asthma, but the spirometry data suggest a restrictive, rather than an obstructive, pattern. “It is possible that early in childhood, the pattern is more obstructive, as in asthma; but [toward] adulthood, the changes become fixed, showing a more restrictive pattern,” she said in a press conference.

Previous data suggested early adulthood mortality is worse in females, but the current results suggested boys and girls alike had a decline in FEV1 of 2.9% predicted per year.

The role of sickle cell genotype, hemoglobin SS or SC, was also evaluated. The SS genotype is more common and considered worse, but has never been examined in terms of lung function. “Children with the hemoglobin SS genotype had a rate of decline in lung function that was twice that of those with the SC genotype,” she said. This novel finding is to be investigated.

TORONTO — Lung function abnormalities are present at age 8 years in children with sickle cell disease, and the subsequent rate of decline is between 2% and 3% a year, according to new data.

“We were aware [of the lung function abnormalities] from cross-sectional studies, but they only look at one time point,” and not across childhood,” Dr. Joanna MacLean told an international conference of the American Thoracic Society.

The pattern of change, whether obstructive or restrictive, in pulmonary function also has not been well delineated in sickle cell disease. The researchers sought clarity because “there is a high mortality in early adulthood in sickle cell disease, with a major contributor being respiratory disease,” said Dr. MacLean of the Hospital for Sick Children, Toronto.

The hospital's sickle cell clinic began requiring pulmonary function testing in 1989. Data for an unselected cohort of 413 children from then until 2005, beginning at age 8 years, were collected and analyzed using linear mixed effects modeling and compared with data for race-matched predicted values and reference equations in the African American population from the third National Health and Nutrition Examination Survey (NHANES III).

The study examined the contributions of age, gender, serum hemoglobin levels, and β-globin genotype on longitudinal changes in spirometry and lung volumes.

The sample consisted of 1,357 pulmonary function test results and 1,129 total lung capacity measurements. About 46% of the records were for males, and the records were evenly distributed across age groups, with a mean age of 12.7 years.

Significant declines were seen in percent predicted values for forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), though not for the FEV1/FVC ratio. Total lung capacity (TLC) and residual volume/TLC ratios demonstrated a similar pattern of change.

There has been considerable interest in the relationship between sickle cell disease and asthma, but the spirometry data suggest a restrictive, rather than an obstructive, pattern. “It is possible that early in childhood, the pattern is more obstructive, as in asthma; but [toward] adulthood, the changes become fixed, showing a more restrictive pattern,” she said in a press conference.

Previous data suggested early adulthood mortality is worse in females, but the current results suggested boys and girls alike had a decline in FEV1 of 2.9% predicted per year.

The role of sickle cell genotype, hemoglobin SS or SC, was also evaluated. The SS genotype is more common and considered worse, but has never been examined in terms of lung function. “Children with the hemoglobin SS genotype had a rate of decline in lung function that was twice that of those with the SC genotype,” she said. This novel finding is to be investigated.

PARIS — Patients with rheumatoid arthritis receiving abatacept showed an increasing magnitude of clinical response between months 6 and 12, Dr. Michael Schiff reported.

In RA, it's important to evaluate efficacy not only at the group level—mean changes that occur in a group as a whole over time—but also at the individual level, and to measure changes in a patient's response over time, Dr. Schiff said in a press conference at the annual European Congress of Rheumatology.

In a post-hoc analysis of ATTEST (Abatacept or infliximab versus placebo, a Trial for Tolerability, Efficacy and Safety in Treating RA), patients who achieved an ACR 20 at 6 months were reevaluated at 12 months to determine whether they further improved, retained, or lost their response.

The larger ATTEST trial, sponsored by Bristol-Myers Squibb Co., included 431 patients who had an inadequate response to methotrexate, and randomized them to abatacept, approximately 10 mg/kg every 4 weeks; infliximab, 3 mg/kg every 8 weeks; or placebo. They also were on background methotrexate, 10-30 mg/week.

At baseline, patients' mean age was 49 years and mean disease duration was 8 years. The majority were women. Mean number of swollen joints was 20, mean number of tender joints was 30, and mean disease activity score (DAS) 28 was 6.4.

At month 6, a total of 32 patients receiving abatacept and 27 patients receiving infliximab had achieved an ACR 20 response, though not ACR 50 or ARC 70 responses. The responses in this subgroup of patients were then analyzed at 12 months.

A similar percentage of patients receiving abatacept and infliximab achieved at least an ACR 50 response at 1 year. A total of 28.1% of patients on abatacept and 29.6% of patients on infliximab continued to improve to this degree, a clinically significant response, said Dr. Schiff, a clinical professor of medicine in the rheumatology division, University of Colorado, Denver.

The proportion of patients who maintained an ACR 20 response at 1 year was 59.4% for abatacept and 44.4% for infliximab, while the proportions who lost their ACR 20 response at 1 year were 12.5% and 25.9%, respectively.

Among the 24 patients treated with abatacept who achieved a low disease activity score (DAS28 below 3.2) at 6 months, 41.7% went on to clinical remission (DAS28 below 2.6) at 1 year. Among the 25 patients treated with infliximab who achieved a low disease activity score at 6 months, 28% went on to remission at 1 year.

A total of 12.5% and 16% of the abatacept- and infliximab-treated patients retained their low disease activity score at 1 year, while 45.8% and 56% lost this response by 1 year.

“These findings highlight the importance of examining clinical benefits at the level of the individual patient,” Dr. Schiff wrote in a poster. “Abatacept has the potential to provide clinical benefits to patients that increase in magnitude over time.”

Dr. Schiff has received research grants and consulting fees from Bristol-Myers Squibb and Centocor.

PARIS — Patients with rheumatoid arthritis receiving abatacept showed an increasing magnitude of clinical response between months 6 and 12, Dr. Michael Schiff reported.

In RA, it's important to evaluate efficacy not only at the group level—mean changes that occur in a group as a whole over time—but also at the individual level, and to measure changes in a patient's response over time, Dr. Schiff said in a press conference at the annual European Congress of Rheumatology.

In a post-hoc analysis of ATTEST (Abatacept or infliximab versus placebo, a Trial for Tolerability, Efficacy and Safety in Treating RA), patients who achieved an ACR 20 at 6 months were reevaluated at 12 months to determine whether they further improved, retained, or lost their response.

The larger ATTEST trial, sponsored by Bristol-Myers Squibb Co., included 431 patients who had an inadequate response to methotrexate, and randomized them to abatacept, approximately 10 mg/kg every 4 weeks; infliximab, 3 mg/kg every 8 weeks; or placebo. They also were on background methotrexate, 10-30 mg/week.

At baseline, patients' mean age was 49 years and mean disease duration was 8 years. The majority were women. Mean number of swollen joints was 20, mean number of tender joints was 30, and mean disease activity score (DAS) 28 was 6.4.

At month 6, a total of 32 patients receiving abatacept and 27 patients receiving infliximab had achieved an ACR 20 response, though not ACR 50 or ARC 70 responses. The responses in this subgroup of patients were then analyzed at 12 months.

A similar percentage of patients receiving abatacept and infliximab achieved at least an ACR 50 response at 1 year. A total of 28.1% of patients on abatacept and 29.6% of patients on infliximab continued to improve to this degree, a clinically significant response, said Dr. Schiff, a clinical professor of medicine in the rheumatology division, University of Colorado, Denver.

The proportion of patients who maintained an ACR 20 response at 1 year was 59.4% for abatacept and 44.4% for infliximab, while the proportions who lost their ACR 20 response at 1 year were 12.5% and 25.9%, respectively.

Among the 24 patients treated with abatacept who achieved a low disease activity score (DAS28 below 3.2) at 6 months, 41.7% went on to clinical remission (DAS28 below 2.6) at 1 year. Among the 25 patients treated with infliximab who achieved a low disease activity score at 6 months, 28% went on to remission at 1 year.

A total of 12.5% and 16% of the abatacept- and infliximab-treated patients retained their low disease activity score at 1 year, while 45.8% and 56% lost this response by 1 year.

“These findings highlight the importance of examining clinical benefits at the level of the individual patient,” Dr. Schiff wrote in a poster. “Abatacept has the potential to provide clinical benefits to patients that increase in magnitude over time.”

Dr. Schiff has received research grants and consulting fees from Bristol-Myers Squibb and Centocor.

PARIS — Patients with rheumatoid arthritis receiving abatacept showed an increasing magnitude of clinical response between months 6 and 12, Dr. Michael Schiff reported.

In RA, it's important to evaluate efficacy not only at the group level—mean changes that occur in a group as a whole over time—but also at the individual level, and to measure changes in a patient's response over time, Dr. Schiff said in a press conference at the annual European Congress of Rheumatology.

In a post-hoc analysis of ATTEST (Abatacept or infliximab versus placebo, a Trial for Tolerability, Efficacy and Safety in Treating RA), patients who achieved an ACR 20 at 6 months were reevaluated at 12 months to determine whether they further improved, retained, or lost their response.

The larger ATTEST trial, sponsored by Bristol-Myers Squibb Co., included 431 patients who had an inadequate response to methotrexate, and randomized them to abatacept, approximately 10 mg/kg every 4 weeks; infliximab, 3 mg/kg every 8 weeks; or placebo. They also were on background methotrexate, 10-30 mg/week.

At baseline, patients' mean age was 49 years and mean disease duration was 8 years. The majority were women. Mean number of swollen joints was 20, mean number of tender joints was 30, and mean disease activity score (DAS) 28 was 6.4.

At month 6, a total of 32 patients receiving abatacept and 27 patients receiving infliximab had achieved an ACR 20 response, though not ACR 50 or ARC 70 responses. The responses in this subgroup of patients were then analyzed at 12 months.

A similar percentage of patients receiving abatacept and infliximab achieved at least an ACR 50 response at 1 year. A total of 28.1% of patients on abatacept and 29.6% of patients on infliximab continued to improve to this degree, a clinically significant response, said Dr. Schiff, a clinical professor of medicine in the rheumatology division, University of Colorado, Denver.

The proportion of patients who maintained an ACR 20 response at 1 year was 59.4% for abatacept and 44.4% for infliximab, while the proportions who lost their ACR 20 response at 1 year were 12.5% and 25.9%, respectively.

Among the 24 patients treated with abatacept who achieved a low disease activity score (DAS28 below 3.2) at 6 months, 41.7% went on to clinical remission (DAS28 below 2.6) at 1 year. Among the 25 patients treated with infliximab who achieved a low disease activity score at 6 months, 28% went on to remission at 1 year.

A total of 12.5% and 16% of the abatacept- and infliximab-treated patients retained their low disease activity score at 1 year, while 45.8% and 56% lost this response by 1 year.

“These findings highlight the importance of examining clinical benefits at the level of the individual patient,” Dr. Schiff wrote in a poster. “Abatacept has the potential to provide clinical benefits to patients that increase in magnitude over time.”

Dr. Schiff has received research grants and consulting fees from Bristol-Myers Squibb and Centocor.

PARIS — The anti-interleukin-6 monoclonal antibody tocilizumab may offer a new alternative for the most refractory patients with rheumatoid arthritis, including those who have failed antitumor necrosis factor drugs.

Both interleukin (IL)-6 and tumor necrosis factor (TNF)-? play major roles in the development and maintenance of rheumatoid arthritis (RA), explained Dr. Paul Emery, Arthritis Research Campaign Professor of Rheumatology and head of the academic section of musculoskeletal diseases at the University of Leeds (England). He gave his presentation at the annual European Congress of Rheumatology.

“While anti-TNF therapies have become established treatments for RA, significant proportions of patients do not achieve an adequate response or become refractory to them,” Dr. Emery said. Inhibiting the ubiquitous cytokine IL-6, which drives the acute phase response among other effects, may offer an additional way of achieving disease control, he said.

In the Research on Actemra Determining Efficacy after Anti-TNF Failure (RADIATE) trial, 498 patients who had previously failed anti-TNF therapy were randomized to receive placebo or tocilizumab in doses of 4 mg/kg or 8 mg/kg administered intravenously every 4 weeks for 24 weeks. A total of 160 were randomized to placebo, 163 to 4 mg/kg, and 175 to 8 mg/kg.

Patients also were receiving stable doses of methotrexate, 10-25 mg/week, and corticosteroids, 10 mg or less/day.

Mean age of patients was 53 years and mean disease duration was 11 years. Most were seropositive, and disease activity scores (DAS) were high, at a mean of 6.8.

Approximately half the patients had failed one anti-TNF agent, another third had failed two, and 12%-18% had failed three prior agents, he said. The study design allowed for escape at 16 weeks. A total of 60% of the controls had withdrawn or were on 8-mg/kg rescue therapy by week 24, as had 34% of the 4-mg group and 25% of the 8-mg group.

ACR 20 responses were seen in 50% of patients receiving the 8-mg/kg dose, according to Dr. Emery, who was lead investigator of the trial, funded by Roche.

Significantly greater improvements were also seen in the 8-mg/kg group on other end points.

“Probably the most impressive finding was that one-third of patients who had previously failed the best we had to offer were able to get into remission, which is a much higher rate than previously has been seen in patients failing TNF,” Dr. Emery said. Remission was defined as a DAS28 score below 2.6.

“This is our worst population, for whom we have no easy options, and the results were equal to or better than what we've seen before,” he added.

Serious adverse events were seen in 11%, 7%, and 6% of the placebo, 4-mg/kg, and 8-mg/kg groups, respectively. Infections occurred in 41%, 47%, and 50% of the placebo, 4-mg, and 8-mg patients, while serious infections were seen in 3%, 2%, and 5%, respectively. There were no opportunistic infections or cases of tuberculosis.

Over the past 12 months, there have been research reports that tocilizumab improves quality of life in RA (RHEUMATOLOGY NEWS, May 2008, p. 6); lessens the articular and systemic manifestations of RA when used with disease-modifying antirheumatic drugs (RHEUMATOLOGY NEWS, January 2008, p. 1); and was beneficial in moderate to severe RA (RHEUMATOLOGY NEWS, October 2007, p. 20). The drug remains investigational both in the United States and Europe.

Dr. Emery has received consulting fees from Roche.

ELSEVIER GLOBAL MEDICAL NEWS

PARIS — The anti-interleukin-6 monoclonal antibody tocilizumab may offer a new alternative for the most refractory patients with rheumatoid arthritis, including those who have failed antitumor necrosis factor drugs.

Both interleukin (IL)-6 and tumor necrosis factor (TNF)-? play major roles in the development and maintenance of rheumatoid arthritis (RA), explained Dr. Paul Emery, Arthritis Research Campaign Professor of Rheumatology and head of the academic section of musculoskeletal diseases at the University of Leeds (England). He gave his presentation at the annual European Congress of Rheumatology.

“While anti-TNF therapies have become established treatments for RA, significant proportions of patients do not achieve an adequate response or become refractory to them,” Dr. Emery said. Inhibiting the ubiquitous cytokine IL-6, which drives the acute phase response among other effects, may offer an additional way of achieving disease control, he said.

In the Research on Actemra Determining Efficacy after Anti-TNF Failure (RADIATE) trial, 498 patients who had previously failed anti-TNF therapy were randomized to receive placebo or tocilizumab in doses of 4 mg/kg or 8 mg/kg administered intravenously every 4 weeks for 24 weeks. A total of 160 were randomized to placebo, 163 to 4 mg/kg, and 175 to 8 mg/kg.

Patients also were receiving stable doses of methotrexate, 10-25 mg/week, and corticosteroids, 10 mg or less/day.

Mean age of patients was 53 years and mean disease duration was 11 years. Most were seropositive, and disease activity scores (DAS) were high, at a mean of 6.8.

Approximately half the patients had failed one anti-TNF agent, another third had failed two, and 12%-18% had failed three prior agents, he said. The study design allowed for escape at 16 weeks. A total of 60% of the controls had withdrawn or were on 8-mg/kg rescue therapy by week 24, as had 34% of the 4-mg group and 25% of the 8-mg group.

ACR 20 responses were seen in 50% of patients receiving the 8-mg/kg dose, according to Dr. Emery, who was lead investigator of the trial, funded by Roche.

Significantly greater improvements were also seen in the 8-mg/kg group on other end points.

“Probably the most impressive finding was that one-third of patients who had previously failed the best we had to offer were able to get into remission, which is a much higher rate than previously has been seen in patients failing TNF,” Dr. Emery said. Remission was defined as a DAS28 score below 2.6.

“This is our worst population, for whom we have no easy options, and the results were equal to or better than what we've seen before,” he added.

Serious adverse events were seen in 11%, 7%, and 6% of the placebo, 4-mg/kg, and 8-mg/kg groups, respectively. Infections occurred in 41%, 47%, and 50% of the placebo, 4-mg, and 8-mg patients, while serious infections were seen in 3%, 2%, and 5%, respectively. There were no opportunistic infections or cases of tuberculosis.

Over the past 12 months, there have been research reports that tocilizumab improves quality of life in RA (RHEUMATOLOGY NEWS, May 2008, p. 6); lessens the articular and systemic manifestations of RA when used with disease-modifying antirheumatic drugs (RHEUMATOLOGY NEWS, January 2008, p. 1); and was beneficial in moderate to severe RA (RHEUMATOLOGY NEWS, October 2007, p. 20). The drug remains investigational both in the United States and Europe.

Dr. Emery has received consulting fees from Roche.

ELSEVIER GLOBAL MEDICAL NEWS

PARIS — The anti-interleukin-6 monoclonal antibody tocilizumab may offer a new alternative for the most refractory patients with rheumatoid arthritis, including those who have failed antitumor necrosis factor drugs.

Both interleukin (IL)-6 and tumor necrosis factor (TNF)-? play major roles in the development and maintenance of rheumatoid arthritis (RA), explained Dr. Paul Emery, Arthritis Research Campaign Professor of Rheumatology and head of the academic section of musculoskeletal diseases at the University of Leeds (England). He gave his presentation at the annual European Congress of Rheumatology.

“While anti-TNF therapies have become established treatments for RA, significant proportions of patients do not achieve an adequate response or become refractory to them,” Dr. Emery said. Inhibiting the ubiquitous cytokine IL-6, which drives the acute phase response among other effects, may offer an additional way of achieving disease control, he said.

In the Research on Actemra Determining Efficacy after Anti-TNF Failure (RADIATE) trial, 498 patients who had previously failed anti-TNF therapy were randomized to receive placebo or tocilizumab in doses of 4 mg/kg or 8 mg/kg administered intravenously every 4 weeks for 24 weeks. A total of 160 were randomized to placebo, 163 to 4 mg/kg, and 175 to 8 mg/kg.

Patients also were receiving stable doses of methotrexate, 10-25 mg/week, and corticosteroids, 10 mg or less/day.

Mean age of patients was 53 years and mean disease duration was 11 years. Most were seropositive, and disease activity scores (DAS) were high, at a mean of 6.8.

Approximately half the patients had failed one anti-TNF agent, another third had failed two, and 12%-18% had failed three prior agents, he said. The study design allowed for escape at 16 weeks. A total of 60% of the controls had withdrawn or were on 8-mg/kg rescue therapy by week 24, as had 34% of the 4-mg group and 25% of the 8-mg group.

ACR 20 responses were seen in 50% of patients receiving the 8-mg/kg dose, according to Dr. Emery, who was lead investigator of the trial, funded by Roche.

Significantly greater improvements were also seen in the 8-mg/kg group on other end points.

“Probably the most impressive finding was that one-third of patients who had previously failed the best we had to offer were able to get into remission, which is a much higher rate than previously has been seen in patients failing TNF,” Dr. Emery said. Remission was defined as a DAS28 score below 2.6.

“This is our worst population, for whom we have no easy options, and the results were equal to or better than what we've seen before,” he added.

Serious adverse events were seen in 11%, 7%, and 6% of the placebo, 4-mg/kg, and 8-mg/kg groups, respectively. Infections occurred in 41%, 47%, and 50% of the placebo, 4-mg, and 8-mg patients, while serious infections were seen in 3%, 2%, and 5%, respectively. There were no opportunistic infections or cases of tuberculosis.

Over the past 12 months, there have been research reports that tocilizumab improves quality of life in RA (RHEUMATOLOGY NEWS, May 2008, p. 6); lessens the articular and systemic manifestations of RA when used with disease-modifying antirheumatic drugs (RHEUMATOLOGY NEWS, January 2008, p. 1); and was beneficial in moderate to severe RA (RHEUMATOLOGY NEWS, October 2007, p. 20). The drug remains investigational both in the United States and Europe.

Dr. Emery has received consulting fees from Roche.

ELSEVIER GLOBAL MEDICAL NEWS

LIVERPOOL, ENGLAND — All patients with newly diagnosed rheumatoid arthritis should have a chest x-ray to rule out rare conditions that can cause arthralgias and inflammation.

Dr. Sarah E. Medley based this advice on a case in which a 52-year-old woman with a 45 pack-year history of smoking presented to the orthopedics department of Queen Elizabeth Hospital, Woolwich, England, with arthralgias affecting the knees, shins, and wrists. Although synovial biopsy of the right knee revealed no synovitis, the patient was diagnosed with rheumatoid arthritis (RA) and treated with methotrexate and then sulfasalazine with prednisone and intramuscular corticosteroids. She was subsequently given an additional diagnosis of facet joint arthritis and given tramadol, meloxicam, and gabapentin for pain.

Rheumatoid factor was negative and erythrocyte sedimentation rate rose from 27 to 101 mm/h, while the woman's disease activity score was very high, at 8.2.

Because conventional treatment was unsuccessful, anti-tumor necrosis factor therapy was planned. Only then was a chest x-ray ordered—as is needed to rule out tuberculosis in patients embarking on biologic therapy. The x-ray revealed a large right apex mass that proved to be a squamous cell carcinoma of the lung. Subsequent resection resulted in rapid and significant improvement in the patient's articular symptoms, and other medications—except analgesics—were stopped because she was receiving adjuvant chemotherapy, Dr. Medley wrote in a poster presented at the annual meeting of the British Society for Rheumatology.

“This case illustrates the need for a chest x-ray in new RA, and emphasizes the fact that atypical unresponsive RA requires review of the diagnosis rather than just treatment escalation,” Dr. Medley wrote.

LIVERPOOL, ENGLAND — All patients with newly diagnosed rheumatoid arthritis should have a chest x-ray to rule out rare conditions that can cause arthralgias and inflammation.

Dr. Sarah E. Medley based this advice on a case in which a 52-year-old woman with a 45 pack-year history of smoking presented to the orthopedics department of Queen Elizabeth Hospital, Woolwich, England, with arthralgias affecting the knees, shins, and wrists. Although synovial biopsy of the right knee revealed no synovitis, the patient was diagnosed with rheumatoid arthritis (RA) and treated with methotrexate and then sulfasalazine with prednisone and intramuscular corticosteroids. She was subsequently given an additional diagnosis of facet joint arthritis and given tramadol, meloxicam, and gabapentin for pain.

Rheumatoid factor was negative and erythrocyte sedimentation rate rose from 27 to 101 mm/h, while the woman's disease activity score was very high, at 8.2.

Because conventional treatment was unsuccessful, anti-tumor necrosis factor therapy was planned. Only then was a chest x-ray ordered—as is needed to rule out tuberculosis in patients embarking on biologic therapy. The x-ray revealed a large right apex mass that proved to be a squamous cell carcinoma of the lung. Subsequent resection resulted in rapid and significant improvement in the patient's articular symptoms, and other medications—except analgesics—were stopped because she was receiving adjuvant chemotherapy, Dr. Medley wrote in a poster presented at the annual meeting of the British Society for Rheumatology.

“This case illustrates the need for a chest x-ray in new RA, and emphasizes the fact that atypical unresponsive RA requires review of the diagnosis rather than just treatment escalation,” Dr. Medley wrote.

LIVERPOOL, ENGLAND — All patients with newly diagnosed rheumatoid arthritis should have a chest x-ray to rule out rare conditions that can cause arthralgias and inflammation.

Dr. Sarah E. Medley based this advice on a case in which a 52-year-old woman with a 45 pack-year history of smoking presented to the orthopedics department of Queen Elizabeth Hospital, Woolwich, England, with arthralgias affecting the knees, shins, and wrists. Although synovial biopsy of the right knee revealed no synovitis, the patient was diagnosed with rheumatoid arthritis (RA) and treated with methotrexate and then sulfasalazine with prednisone and intramuscular corticosteroids. She was subsequently given an additional diagnosis of facet joint arthritis and given tramadol, meloxicam, and gabapentin for pain.

Rheumatoid factor was negative and erythrocyte sedimentation rate rose from 27 to 101 mm/h, while the woman's disease activity score was very high, at 8.2.

Because conventional treatment was unsuccessful, anti-tumor necrosis factor therapy was planned. Only then was a chest x-ray ordered—as is needed to rule out tuberculosis in patients embarking on biologic therapy. The x-ray revealed a large right apex mass that proved to be a squamous cell carcinoma of the lung. Subsequent resection resulted in rapid and significant improvement in the patient's articular symptoms, and other medications—except analgesics—were stopped because she was receiving adjuvant chemotherapy, Dr. Medley wrote in a poster presented at the annual meeting of the British Society for Rheumatology.

“This case illustrates the need for a chest x-ray in new RA, and emphasizes the fact that atypical unresponsive RA requires review of the diagnosis rather than just treatment escalation,” Dr. Medley wrote.

LIVERPOOL, ENGLAND — Rituximab has been used successfully in a real-world setting as a first-line biologic therapy for rheumatoid arthritis that does not respond to conventional disease-modifying drugs, Dr. Ai Lyn Tan reported at the annual meeting of the British Society for Rheumatology.

Rituximab is licensed in the United Kingdom for the treatment of adults with rheumatoid arthritis (RA) who have had an inadequate response to, or who are intolerant of, conventional disease-modifying anti-rheumatic drugs (DMARDs) and to one or more tumor necrosis factor (TNF) inhibitors. In the United States, it is licensed for use in combination with methotrexate for management of moderately to severely active RA that has not responded to treatment with one or more anti-TNF agents.

Dr. Tan and her colleagues at the University of Leeds (England) and Chapel Allerton Hospital, Leeds, have studied a total of 39 patients who had failed at least one DMARD and who received two initial infusions of rituximab 2 weeks apart. In 17 patients, the doses were 1,000 mg each, and in 22, the doses were 500 mg each.

Two-thirds of the patients were women. Their median age was 58 years and median disease duration was 7 years. Thirty were rheumatoid factor (RF) positive at baseline, and 16 were also antinuclear antibody (ANA) positive. Clinical outcome data were available for 37 patients and safety data for all 39.

Clinical assessments using the Disease Activity Score (DAS) 28 and EULAR response criteria were done at 3, 6, 9, and 12 months. The EULAR response criteria use the change in DAS and the level of DAS achieved to classify patients as good, moderate, or nonresponders.

At all time points, there was a significant improvement in DAS28 (see the chart). EULAR good responses were seen in 40% of patients at 3 months and in 50% of patients at 12 months, while overall EULAR responses were seen in 88% and 77%, respectively, at those time points.

By 6 months, ANA became negative in 40% of patients in whom it had been positive at baseline, and in 88% of RF-positive patients the antibody level had fallen. Four of the previously RF-positive patients became seronegative by 6 months, and these reductions were sustained at 12 months, Dr. Tan wrote in a poster presentation.

Slightly better responses were seen in patients who received the higher dose, with 82% in the 500-mg group and 94% of those in the 1,000-mg group achieving EULAR responses. Nonetheless, she suggested that it might be “prudent” to start on lower doses since treatment is likely to be needed long term.

Thus far, 25 patients have been re-treated, at a median of 13 months after the initial infusions, and 7 have received a third treatment, at a median of 11 months after the second treatment. Two patients were switched to anti-TNF therapy after early treatment failure, and a third was switched after an allergic reaction to the second infusion of rituximab, said Dr. Tan, who declared no conflicts of interest.

A 67-year-old patient with preexisting lung disease died 3 months after treatment from presumed bilateral bronchopneumonia and possible methotrexate pneumonitis, and a 61-year-old man died of a myocardial infarction while awaiting coronary angiography for angina pectoris. The outcome was not considered related to therapy.

In an interview, Dr. Tan said the data showed rituximab is effective as first-line therapy for severe RA. “This is important because it can be used in patients in whom the TNF blockers are contraindicated.

ELSEVIER GLOBAL MEDICAL NEWS

LIVERPOOL, ENGLAND — Rituximab has been used successfully in a real-world setting as a first-line biologic therapy for rheumatoid arthritis that does not respond to conventional disease-modifying drugs, Dr. Ai Lyn Tan reported at the annual meeting of the British Society for Rheumatology.

Rituximab is licensed in the United Kingdom for the treatment of adults with rheumatoid arthritis (RA) who have had an inadequate response to, or who are intolerant of, conventional disease-modifying anti-rheumatic drugs (DMARDs) and to one or more tumor necrosis factor (TNF) inhibitors. In the United States, it is licensed for use in combination with methotrexate for management of moderately to severely active RA that has not responded to treatment with one or more anti-TNF agents.

Dr. Tan and her colleagues at the University of Leeds (England) and Chapel Allerton Hospital, Leeds, have studied a total of 39 patients who had failed at least one DMARD and who received two initial infusions of rituximab 2 weeks apart. In 17 patients, the doses were 1,000 mg each, and in 22, the doses were 500 mg each.

Two-thirds of the patients were women. Their median age was 58 years and median disease duration was 7 years. Thirty were rheumatoid factor (RF) positive at baseline, and 16 were also antinuclear antibody (ANA) positive. Clinical outcome data were available for 37 patients and safety data for all 39.

Clinical assessments using the Disease Activity Score (DAS) 28 and EULAR response criteria were done at 3, 6, 9, and 12 months. The EULAR response criteria use the change in DAS and the level of DAS achieved to classify patients as good, moderate, or nonresponders.

At all time points, there was a significant improvement in DAS28 (see the chart). EULAR good responses were seen in 40% of patients at 3 months and in 50% of patients at 12 months, while overall EULAR responses were seen in 88% and 77%, respectively, at those time points.

By 6 months, ANA became negative in 40% of patients in whom it had been positive at baseline, and in 88% of RF-positive patients the antibody level had fallen. Four of the previously RF-positive patients became seronegative by 6 months, and these reductions were sustained at 12 months, Dr. Tan wrote in a poster presentation.

Slightly better responses were seen in patients who received the higher dose, with 82% in the 500-mg group and 94% of those in the 1,000-mg group achieving EULAR responses. Nonetheless, she suggested that it might be “prudent” to start on lower doses since treatment is likely to be needed long term.

Thus far, 25 patients have been re-treated, at a median of 13 months after the initial infusions, and 7 have received a third treatment, at a median of 11 months after the second treatment. Two patients were switched to anti-TNF therapy after early treatment failure, and a third was switched after an allergic reaction to the second infusion of rituximab, said Dr. Tan, who declared no conflicts of interest.

A 67-year-old patient with preexisting lung disease died 3 months after treatment from presumed bilateral bronchopneumonia and possible methotrexate pneumonitis, and a 61-year-old man died of a myocardial infarction while awaiting coronary angiography for angina pectoris. The outcome was not considered related to therapy.

In an interview, Dr. Tan said the data showed rituximab is effective as first-line therapy for severe RA. “This is important because it can be used in patients in whom the TNF blockers are contraindicated.

ELSEVIER GLOBAL MEDICAL NEWS

LIVERPOOL, ENGLAND — Rituximab has been used successfully in a real-world setting as a first-line biologic therapy for rheumatoid arthritis that does not respond to conventional disease-modifying drugs, Dr. Ai Lyn Tan reported at the annual meeting of the British Society for Rheumatology.

Rituximab is licensed in the United Kingdom for the treatment of adults with rheumatoid arthritis (RA) who have had an inadequate response to, or who are intolerant of, conventional disease-modifying anti-rheumatic drugs (DMARDs) and to one or more tumor necrosis factor (TNF) inhibitors. In the United States, it is licensed for use in combination with methotrexate for management of moderately to severely active RA that has not responded to treatment with one or more anti-TNF agents.

Dr. Tan and her colleagues at the University of Leeds (England) and Chapel Allerton Hospital, Leeds, have studied a total of 39 patients who had failed at least one DMARD and who received two initial infusions of rituximab 2 weeks apart. In 17 patients, the doses were 1,000 mg each, and in 22, the doses were 500 mg each.

Two-thirds of the patients were women. Their median age was 58 years and median disease duration was 7 years. Thirty were rheumatoid factor (RF) positive at baseline, and 16 were also antinuclear antibody (ANA) positive. Clinical outcome data were available for 37 patients and safety data for all 39.

Clinical assessments using the Disease Activity Score (DAS) 28 and EULAR response criteria were done at 3, 6, 9, and 12 months. The EULAR response criteria use the change in DAS and the level of DAS achieved to classify patients as good, moderate, or nonresponders.

At all time points, there was a significant improvement in DAS28 (see the chart). EULAR good responses were seen in 40% of patients at 3 months and in 50% of patients at 12 months, while overall EULAR responses were seen in 88% and 77%, respectively, at those time points.

By 6 months, ANA became negative in 40% of patients in whom it had been positive at baseline, and in 88% of RF-positive patients the antibody level had fallen. Four of the previously RF-positive patients became seronegative by 6 months, and these reductions were sustained at 12 months, Dr. Tan wrote in a poster presentation.

Slightly better responses were seen in patients who received the higher dose, with 82% in the 500-mg group and 94% of those in the 1,000-mg group achieving EULAR responses. Nonetheless, she suggested that it might be “prudent” to start on lower doses since treatment is likely to be needed long term.

Thus far, 25 patients have been re-treated, at a median of 13 months after the initial infusions, and 7 have received a third treatment, at a median of 11 months after the second treatment. Two patients were switched to anti-TNF therapy after early treatment failure, and a third was switched after an allergic reaction to the second infusion of rituximab, said Dr. Tan, who declared no conflicts of interest.

A 67-year-old patient with preexisting lung disease died 3 months after treatment from presumed bilateral bronchopneumonia and possible methotrexate pneumonitis, and a 61-year-old man died of a myocardial infarction while awaiting coronary angiography for angina pectoris. The outcome was not considered related to therapy.

In an interview, Dr. Tan said the data showed rituximab is effective as first-line therapy for severe RA. “This is important because it can be used in patients in whom the TNF blockers are contraindicated.

ELSEVIER GLOBAL MEDICAL NEWS

LIVERPOOL, ENGLAND — Consumption of soft drinks containing fructose may underlie the sharp increase in gout in American adults that has occurred in recent decades, Dr. Hyon K. Choi said at the annual meeting of the British Society for Rheumatology.

Since 1967, when high-fructose corn syrup became commercially available and began to be used for sweetening soft drinks, there has been a 61% increase in the consumption of these beverages and a doubling of the incidence and prevalence of gout, particularly in men.

Conventional strategies for the prevention of gout have emphasized limiting consumption of purine-rich foods because uric acid is a breakdown product of purine. But fructose also can increase uric acid. The process involves the breakdown of adenosine triphosphate to adenosine monophosphate, a uric acid precursor, said Dr. Choi, a rheumatologist at the University of British Columbia, Vancouver.

Fructose also contributes to impaired glucose tolerance and increases insulin resistance and hyperinsulinemia, which could elevate serum uric acid levels.

Prospective studies have shown that sugary soft drinks contribute significantly to gout—as well as obesity, type 2 diabetes, and metabolic syndrome, he said.

In the large, ongoing health-professionals follow-up study of more than 51,000 men aged 40–75 years who answered dietary questionnaires and have been followed since 1986, a total of 755 new cases of gout have been diagnosed. The multivariate relative risk of gout for five to six servings of sugary soft drinks a week was 1.29; this rose to 1.85 for two or more servings a day, representing an 85% increase in incident gout in the highest consumers (BMJ 2008;336:309–12).

In another study that includes 14,761 participants aged 20 years and older from the third National Health and Nutrition Examination Survey (NHANES-III), serum uric-acid levels increased significantly with increasing sugary soft-drink consumption, with multivariate odds ratios for hyperuricemia being 1.82 in those who consumed four or more servings a day (Arthritis Rheum. 2008;59:109–16).

In both of these studies, the associations were independent of risk factors for gout including alcohol use, hypertension, and body mass index.

Data from NHANES-III, which is considered a nationally representative sample, also suggest that coffee may be protective, but only if it is drunk in large quantities, he said. After adjustment for age and sex, serum uric-acid levels in those drinking six cups of coffee a day were significantly lower by 0.43 mg/dL than in those who did not drink coffee (Arthritis Rheum. 2007;57:816–21).

The effect was not related to caffeine intake, as modest effects were seen with decaffeinated coffee, and none were seen in tea drinkers. “It could derive from other components in coffee such as chlorogenic acid or noncaffeine xanthines,” he said.

In conclusion, patients at risk for gout should continue to emphasize limitations on purine-rich foods such as beer and certain meats. Purine-rich vegetables such as spinach and beans do not seem to elevate uric-acid levels, and need not be avoided.

Sugary soft drinks and other processed foods containing fructose should be avoided, not only for gout prevention but for prevention of the common comorbidities such as hypertension and obesity, he said.

Dr. Choi's work has been funded by the National Institutes of Health and the Arthritis Society of Canada. He said he has served on the advisory boards for TAP Pharmaceutical Products Inc. and Savient Pharmaceuticals Inc.

LIVERPOOL, ENGLAND — Consumption of soft drinks containing fructose may underlie the sharp increase in gout in American adults that has occurred in recent decades, Dr. Hyon K. Choi said at the annual meeting of the British Society for Rheumatology.

Since 1967, when high-fructose corn syrup became commercially available and began to be used for sweetening soft drinks, there has been a 61% increase in the consumption of these beverages and a doubling of the incidence and prevalence of gout, particularly in men.

Conventional strategies for the prevention of gout have emphasized limiting consumption of purine-rich foods because uric acid is a breakdown product of purine. But fructose also can increase uric acid. The process involves the breakdown of adenosine triphosphate to adenosine monophosphate, a uric acid precursor, said Dr. Choi, a rheumatologist at the University of British Columbia, Vancouver.

Fructose also contributes to impaired glucose tolerance and increases insulin resistance and hyperinsulinemia, which could elevate serum uric acid levels.

Prospective studies have shown that sugary soft drinks contribute significantly to gout—as well as obesity, type 2 diabetes, and metabolic syndrome, he said.

In the large, ongoing health-professionals follow-up study of more than 51,000 men aged 40–75 years who answered dietary questionnaires and have been followed since 1986, a total of 755 new cases of gout have been diagnosed. The multivariate relative risk of gout for five to six servings of sugary soft drinks a week was 1.29; this rose to 1.85 for two or more servings a day, representing an 85% increase in incident gout in the highest consumers (BMJ 2008;336:309–12).

In another study that includes 14,761 participants aged 20 years and older from the third National Health and Nutrition Examination Survey (NHANES-III), serum uric-acid levels increased significantly with increasing sugary soft-drink consumption, with multivariate odds ratios for hyperuricemia being 1.82 in those who consumed four or more servings a day (Arthritis Rheum. 2008;59:109–16).

In both of these studies, the associations were independent of risk factors for gout including alcohol use, hypertension, and body mass index.

Data from NHANES-III, which is considered a nationally representative sample, also suggest that coffee may be protective, but only if it is drunk in large quantities, he said. After adjustment for age and sex, serum uric-acid levels in those drinking six cups of coffee a day were significantly lower by 0.43 mg/dL than in those who did not drink coffee (Arthritis Rheum. 2007;57:816–21).

The effect was not related to caffeine intake, as modest effects were seen with decaffeinated coffee, and none were seen in tea drinkers. “It could derive from other components in coffee such as chlorogenic acid or noncaffeine xanthines,” he said.

In conclusion, patients at risk for gout should continue to emphasize limitations on purine-rich foods such as beer and certain meats. Purine-rich vegetables such as spinach and beans do not seem to elevate uric-acid levels, and need not be avoided.

Sugary soft drinks and other processed foods containing fructose should be avoided, not only for gout prevention but for prevention of the common comorbidities such as hypertension and obesity, he said.

Dr. Choi's work has been funded by the National Institutes of Health and the Arthritis Society of Canada. He said he has served on the advisory boards for TAP Pharmaceutical Products Inc. and Savient Pharmaceuticals Inc.

LIVERPOOL, ENGLAND — Consumption of soft drinks containing fructose may underlie the sharp increase in gout in American adults that has occurred in recent decades, Dr. Hyon K. Choi said at the annual meeting of the British Society for Rheumatology.

Since 1967, when high-fructose corn syrup became commercially available and began to be used for sweetening soft drinks, there has been a 61% increase in the consumption of these beverages and a doubling of the incidence and prevalence of gout, particularly in men.

Conventional strategies for the prevention of gout have emphasized limiting consumption of purine-rich foods because uric acid is a breakdown product of purine. But fructose also can increase uric acid. The process involves the breakdown of adenosine triphosphate to adenosine monophosphate, a uric acid precursor, said Dr. Choi, a rheumatologist at the University of British Columbia, Vancouver.

Fructose also contributes to impaired glucose tolerance and increases insulin resistance and hyperinsulinemia, which could elevate serum uric acid levels.

Prospective studies have shown that sugary soft drinks contribute significantly to gout—as well as obesity, type 2 diabetes, and metabolic syndrome, he said.

In the large, ongoing health-professionals follow-up study of more than 51,000 men aged 40–75 years who answered dietary questionnaires and have been followed since 1986, a total of 755 new cases of gout have been diagnosed. The multivariate relative risk of gout for five to six servings of sugary soft drinks a week was 1.29; this rose to 1.85 for two or more servings a day, representing an 85% increase in incident gout in the highest consumers (BMJ 2008;336:309–12).

In another study that includes 14,761 participants aged 20 years and older from the third National Health and Nutrition Examination Survey (NHANES-III), serum uric-acid levels increased significantly with increasing sugary soft-drink consumption, with multivariate odds ratios for hyperuricemia being 1.82 in those who consumed four or more servings a day (Arthritis Rheum. 2008;59:109–16).

In both of these studies, the associations were independent of risk factors for gout including alcohol use, hypertension, and body mass index.

Data from NHANES-III, which is considered a nationally representative sample, also suggest that coffee may be protective, but only if it is drunk in large quantities, he said. After adjustment for age and sex, serum uric-acid levels in those drinking six cups of coffee a day were significantly lower by 0.43 mg/dL than in those who did not drink coffee (Arthritis Rheum. 2007;57:816–21).

The effect was not related to caffeine intake, as modest effects were seen with decaffeinated coffee, and none were seen in tea drinkers. “It could derive from other components in coffee such as chlorogenic acid or noncaffeine xanthines,” he said.

In conclusion, patients at risk for gout should continue to emphasize limitations on purine-rich foods such as beer and certain meats. Purine-rich vegetables such as spinach and beans do not seem to elevate uric-acid levels, and need not be avoided.

Sugary soft drinks and other processed foods containing fructose should be avoided, not only for gout prevention but for prevention of the common comorbidities such as hypertension and obesity, he said.

Dr. Choi's work has been funded by the National Institutes of Health and the Arthritis Society of Canada. He said he has served on the advisory boards for TAP Pharmaceutical Products Inc. and Savient Pharmaceuticals Inc.

TORONTO — Treatment with a proton pump inhibitor did not improve asthma control in patients with poorly controlled asthma and minimal or no symptoms of gastroesophageal reflux, according to results from a large study presented at an international conference of the American Thoracic Society.

Gastroesophageal reflux disease (GERD) is a common problem in patients with asthma, with small studies reporting a prevalence of reflux in 32%–84% of asthmatics. Proton pump inhibitor (PPI) therapy is commonly added to therapy in asthma, adding to the overall cost of treatment, but the effect of suppression of gastric acid on asthma symptoms remains unclear, according to Dr. Mario Castro of Washington University School, St. Louis.

Uncertainty about the role of GERD in asthma derives from observations that about half of asthmatics without symptoms of GERD have been shown to have abnormal reflux and about half of asthmatics who have abnormal reflux shown on pH probe studies do not have symptoms of the disease, Dr. Castro explained. “GERD symptoms can mimic symptoms of asthma, and we wanted to know how to distinguish them and how best to treat them.”

Recent guidelines released by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health suggested that, even in the absence of GERD symptoms, consideration should be given to evaluation and possible treatment with PPI for patients with poorly controlled asthma. This was a consensus-based recommendation.

To gain additional data to strengthen the recommendation, the Study of Acid Reflux in Asthma (SARA) was undertaken with funding from the NHLBI and conducted by the American Lung Association's asthma clinical research centers, a national 20-center network dedicated to improving asthma care.

“SARA included only patients with minimal or no symptoms of GERD, because we felt that any patient with moderate or severe GERD should, by definition, be receiving a PPI—and, in this trial, there was the possibility that they would receive placebo,” Dr. Castro said.

Aside from determining whether PPI therapy could improve asthma symptoms in those patients, SARA also sought to determine whether ambulatory pH probe monitoring could identify patients with asymptomatic GERD who might benefit from suppression of gastric acid.

The study design called for a 2- to 8-week run-in period, during which patients underwent pH probe monitoring and, if not contraindicated, methacholine challenge testing. They then were randomized to receive esomeprazole, 40 mg/day, along with stable doses of inhaled corticosteroids (equivalent to at least 400 mg fluticasone/day) and long-acting β-agonists if needed.

Poorly controlled asthma was defined as two or more occasions of a 30% or greater decline in peak expiratory flow from baseline, the need for oral prednisone, the requirement for acute intervention (an emergency department visit), or the need for more than four puffs of rescue medication.

Another investigator, Dr. W. Gerald Teague of the pediatric asthma center at Emory University, Atlanta, described the participants' baseline characteristics. “A total of 412 patients were randomized, … data from 10 patients were lost in Hurricane Katrina.” Of those remaining, 199 received placebo and 203 received esomeprazole.

Overall, the groups were comparable. Mean age was 42 years, and 50% were white and 38% were black. In the placebo group, 28% were male and 20% were former smokers. In the esomeprazole group, 36% were male and 15% were former smokers. About half of the patients in both groups had required use of rescue medications during the previous year, and the same number had required courses of oral prednisone. Asthma control also was equivalent in the two groups, with a mean Asthma Control Questionnaire (ACQ) score of 1.9 in the placebo group and 1.8 in the PPI group.

Lung function also was comparable, with a forced expiratory volume in 1 second (FEV1) at 78% of predicted in the placebo group and 76% of predicted in the esomeprazole group. There were no differences in post-albuterol response, forced vital capacity, or bronchial hyperresponsiveness. On pH probe testing, 40% of patients in both groups were positive for GERD.

“We were surprised, but when baseline asthma characteristics were analyzed according to whether or not patients were positive for GERD on pH probe testing, there was very little effect,” Dr. Teague said. In both GERD and non-GERD groups, 80% had required rescue medicine, ACQ scores were 1.9, and Asthma Quality of Life scores were 4.6, he reported.

“Overall, we saw no treatment effect in either group,” Dr. John G. Mastronarde, a pulmonologist at Ohio State University Medical Center, Columbus, and director of the university's asthma center. The number of episodes of decrease in peak flow was 1.7/person per year in the placebo group and 2.1/person per year in the esomeprazole group. The number of episodes requiring urgent care was 0.7 in the placebo group and 0.6 in the esomeprazole group.

Some study data have suggested certain subgroups, such as patients with episodes of nocturnal awakening and those with a body mass index greater than 30 kg/m

Lung function as measured on FEV1, peak flow, and tests of bronchial hyperresponsiveness also showed no effects of treatment, nor did patient-centered outcomes such as ACQ scores, even in patients with positive pH probe tests, Dr. Mastronarde said.

“In summary, asymptomatic GERD is common in patients with poorly controlled asthma, but PPI therapy with esomeprazole does not improve asthma control or lung function in patients with minimal or absent symptoms of GERD. … Ambulatory pH probe testing did not seem to identify any subgroups of patients who might benefit from PPI testing in terms of asthma control,” he said.

“The NIH guidelines suggest that we consider evaluation and treatment in patients with poorly controlled asthma on adequate controllers even without symptoms of GERD, but this study would suggest that PPI therapy has no effect on control and is not indicated,” Dr. Mastronarde noted. “Also, there doesn't seem to be any reason to do pH probe testing on poorly controlled asthmatics, because even if they are positive, it doesn't predict who will respond to PPI treatment.”

TORONTO — Treatment with a proton pump inhibitor did not improve asthma control in patients with poorly controlled asthma and minimal or no symptoms of gastroesophageal reflux, according to results from a large study presented at an international conference of the American Thoracic Society.

Gastroesophageal reflux disease (GERD) is a common problem in patients with asthma, with small studies reporting a prevalence of reflux in 32%–84% of asthmatics. Proton pump inhibitor (PPI) therapy is commonly added to therapy in asthma, adding to the overall cost of treatment, but the effect of suppression of gastric acid on asthma symptoms remains unclear, according to Dr. Mario Castro of Washington University School, St. Louis.

Uncertainty about the role of GERD in asthma derives from observations that about half of asthmatics without symptoms of GERD have been shown to have abnormal reflux and about half of asthmatics who have abnormal reflux shown on pH probe studies do not have symptoms of the disease, Dr. Castro explained. “GERD symptoms can mimic symptoms of asthma, and we wanted to know how to distinguish them and how best to treat them.”

Recent guidelines released by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health suggested that, even in the absence of GERD symptoms, consideration should be given to evaluation and possible treatment with PPI for patients with poorly controlled asthma. This was a consensus-based recommendation.

To gain additional data to strengthen the recommendation, the Study of Acid Reflux in Asthma (SARA) was undertaken with funding from the NHLBI and conducted by the American Lung Association's asthma clinical research centers, a national 20-center network dedicated to improving asthma care.

“SARA included only patients with minimal or no symptoms of GERD, because we felt that any patient with moderate or severe GERD should, by definition, be receiving a PPI—and, in this trial, there was the possibility that they would receive placebo,” Dr. Castro said.

Aside from determining whether PPI therapy could improve asthma symptoms in those patients, SARA also sought to determine whether ambulatory pH probe monitoring could identify patients with asymptomatic GERD who might benefit from suppression of gastric acid.

The study design called for a 2- to 8-week run-in period, during which patients underwent pH probe monitoring and, if not contraindicated, methacholine challenge testing. They then were randomized to receive esomeprazole, 40 mg/day, along with stable doses of inhaled corticosteroids (equivalent to at least 400 mg fluticasone/day) and long-acting β-agonists if needed.

Poorly controlled asthma was defined as two or more occasions of a 30% or greater decline in peak expiratory flow from baseline, the need for oral prednisone, the requirement for acute intervention (an emergency department visit), or the need for more than four puffs of rescue medication.

Another investigator, Dr. W. Gerald Teague of the pediatric asthma center at Emory University, Atlanta, described the participants' baseline characteristics. “A total of 412 patients were randomized, … data from 10 patients were lost in Hurricane Katrina.” Of those remaining, 199 received placebo and 203 received esomeprazole.

Overall, the groups were comparable. Mean age was 42 years, and 50% were white and 38% were black. In the placebo group, 28% were male and 20% were former smokers. In the esomeprazole group, 36% were male and 15% were former smokers. About half of the patients in both groups had required use of rescue medications during the previous year, and the same number had required courses of oral prednisone. Asthma control also was equivalent in the two groups, with a mean Asthma Control Questionnaire (ACQ) score of 1.9 in the placebo group and 1.8 in the PPI group.

Lung function also was comparable, with a forced expiratory volume in 1 second (FEV1) at 78% of predicted in the placebo group and 76% of predicted in the esomeprazole group. There were no differences in post-albuterol response, forced vital capacity, or bronchial hyperresponsiveness. On pH probe testing, 40% of patients in both groups were positive for GERD.

“We were surprised, but when baseline asthma characteristics were analyzed according to whether or not patients were positive for GERD on pH probe testing, there was very little effect,” Dr. Teague said. In both GERD and non-GERD groups, 80% had required rescue medicine, ACQ scores were 1.9, and Asthma Quality of Life scores were 4.6, he reported.

“Overall, we saw no treatment effect in either group,” Dr. John G. Mastronarde, a pulmonologist at Ohio State University Medical Center, Columbus, and director of the university's asthma center. The number of episodes of decrease in peak flow was 1.7/person per year in the placebo group and 2.1/person per year in the esomeprazole group. The number of episodes requiring urgent care was 0.7 in the placebo group and 0.6 in the esomeprazole group.

Some study data have suggested certain subgroups, such as patients with episodes of nocturnal awakening and those with a body mass index greater than 30 kg/m

Lung function as measured on FEV1, peak flow, and tests of bronchial hyperresponsiveness also showed no effects of treatment, nor did patient-centered outcomes such as ACQ scores, even in patients with positive pH probe tests, Dr. Mastronarde said.

“In summary, asymptomatic GERD is common in patients with poorly controlled asthma, but PPI therapy with esomeprazole does not improve asthma control or lung function in patients with minimal or absent symptoms of GERD. … Ambulatory pH probe testing did not seem to identify any subgroups of patients who might benefit from PPI testing in terms of asthma control,” he said.

“The NIH guidelines suggest that we consider evaluation and treatment in patients with poorly controlled asthma on adequate controllers even without symptoms of GERD, but this study would suggest that PPI therapy has no effect on control and is not indicated,” Dr. Mastronarde noted. “Also, there doesn't seem to be any reason to do pH probe testing on poorly controlled asthmatics, because even if they are positive, it doesn't predict who will respond to PPI treatment.”

TORONTO — Treatment with a proton pump inhibitor did not improve asthma control in patients with poorly controlled asthma and minimal or no symptoms of gastroesophageal reflux, according to results from a large study presented at an international conference of the American Thoracic Society.

Gastroesophageal reflux disease (GERD) is a common problem in patients with asthma, with small studies reporting a prevalence of reflux in 32%–84% of asthmatics. Proton pump inhibitor (PPI) therapy is commonly added to therapy in asthma, adding to the overall cost of treatment, but the effect of suppression of gastric acid on asthma symptoms remains unclear, according to Dr. Mario Castro of Washington University School, St. Louis.

Uncertainty about the role of GERD in asthma derives from observations that about half of asthmatics without symptoms of GERD have been shown to have abnormal reflux and about half of asthmatics who have abnormal reflux shown on pH probe studies do not have symptoms of the disease, Dr. Castro explained. “GERD symptoms can mimic symptoms of asthma, and we wanted to know how to distinguish them and how best to treat them.”

Recent guidelines released by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health suggested that, even in the absence of GERD symptoms, consideration should be given to evaluation and possible treatment with PPI for patients with poorly controlled asthma. This was a consensus-based recommendation.

To gain additional data to strengthen the recommendation, the Study of Acid Reflux in Asthma (SARA) was undertaken with funding from the NHLBI and conducted by the American Lung Association's asthma clinical research centers, a national 20-center network dedicated to improving asthma care.

“SARA included only patients with minimal or no symptoms of GERD, because we felt that any patient with moderate or severe GERD should, by definition, be receiving a PPI—and, in this trial, there was the possibility that they would receive placebo,” Dr. Castro said.

Aside from determining whether PPI therapy could improve asthma symptoms in those patients, SARA also sought to determine whether ambulatory pH probe monitoring could identify patients with asymptomatic GERD who might benefit from suppression of gastric acid.

The study design called for a 2- to 8-week run-in period, during which patients underwent pH probe monitoring and, if not contraindicated, methacholine challenge testing. They then were randomized to receive esomeprazole, 40 mg/day, along with stable doses of inhaled corticosteroids (equivalent to at least 400 mg fluticasone/day) and long-acting β-agonists if needed.

Poorly controlled asthma was defined as two or more occasions of a 30% or greater decline in peak expiratory flow from baseline, the need for oral prednisone, the requirement for acute intervention (an emergency department visit), or the need for more than four puffs of rescue medication.

Another investigator, Dr. W. Gerald Teague of the pediatric asthma center at Emory University, Atlanta, described the participants' baseline characteristics. “A total of 412 patients were randomized, … data from 10 patients were lost in Hurricane Katrina.” Of those remaining, 199 received placebo and 203 received esomeprazole.

Overall, the groups were comparable. Mean age was 42 years, and 50% were white and 38% were black. In the placebo group, 28% were male and 20% were former smokers. In the esomeprazole group, 36% were male and 15% were former smokers. About half of the patients in both groups had required use of rescue medications during the previous year, and the same number had required courses of oral prednisone. Asthma control also was equivalent in the two groups, with a mean Asthma Control Questionnaire (ACQ) score of 1.9 in the placebo group and 1.8 in the PPI group.

Lung function also was comparable, with a forced expiratory volume in 1 second (FEV1) at 78% of predicted in the placebo group and 76% of predicted in the esomeprazole group. There were no differences in post-albuterol response, forced vital capacity, or bronchial hyperresponsiveness. On pH probe testing, 40% of patients in both groups were positive for GERD.

“We were surprised, but when baseline asthma characteristics were analyzed according to whether or not patients were positive for GERD on pH probe testing, there was very little effect,” Dr. Teague said. In both GERD and non-GERD groups, 80% had required rescue medicine, ACQ scores were 1.9, and Asthma Quality of Life scores were 4.6, he reported.

“Overall, we saw no treatment effect in either group,” Dr. John G. Mastronarde, a pulmonologist at Ohio State University Medical Center, Columbus, and director of the university's asthma center. The number of episodes of decrease in peak flow was 1.7/person per year in the placebo group and 2.1/person per year in the esomeprazole group. The number of episodes requiring urgent care was 0.7 in the placebo group and 0.6 in the esomeprazole group.

Some study data have suggested certain subgroups, such as patients with episodes of nocturnal awakening and those with a body mass index greater than 30 kg/m

Lung function as measured on FEV1, peak flow, and tests of bronchial hyperresponsiveness also showed no effects of treatment, nor did patient-centered outcomes such as ACQ scores, even in patients with positive pH probe tests, Dr. Mastronarde said.

“In summary, asymptomatic GERD is common in patients with poorly controlled asthma, but PPI therapy with esomeprazole does not improve asthma control or lung function in patients with minimal or absent symptoms of GERD. … Ambulatory pH probe testing did not seem to identify any subgroups of patients who might benefit from PPI testing in terms of asthma control,” he said.

“The NIH guidelines suggest that we consider evaluation and treatment in patients with poorly controlled asthma on adequate controllers even without symptoms of GERD, but this study would suggest that PPI therapy has no effect on control and is not indicated,” Dr. Mastronarde noted. “Also, there doesn't seem to be any reason to do pH probe testing on poorly controlled asthmatics, because even if they are positive, it doesn't predict who will respond to PPI treatment.”