Showing papers in "Thorax in 2007"

Worldwide trends in the prevalence of asthma symptoms: phase III of the International Study of Asthma and Allergies in Childhood (ISAAC)

Abstract: BACKGROUND: Phase I of the International Study of Asthma and Allergies in Childhood (ISAAC) was designed to allow worldwide comparisons of the prevalence of asthma symptoms. In phase III the phase I survey was repeated in order to assess changes over time. METHODS: The phase I survey was repeated after an interval of 5-10 years in 106 centres in 56 countries in children aged 13-14 years (n = 304,679) and in 66 centres in 37 countries in children aged 6-7 years (n = 193,404). RESULTS: The mean symptom prevalence of current wheeze in the last 12 months changed slightly from 13.2% to 13.7% in the 13-14 year age group (mean increase of 0.06% per year) and from 11.1% to 11.6% in the 6-7 year age group (mean increase of 0.13% per year). There was also little change in the mean symptom prevalence of severe asthma or the symptom prevalence measured with the asthma video questionnaire. However, the time trends in asthma symptom prevalence showed different regional patterns. In Western Europe, current wheeze decreased by 0.07% per year in children aged 13-14 years but increased by 0.20% per year in children aged 6-7 years. The corresponding findings per year for the other regions in children aged 13-14 years and 6-7 years, respectively, were: Oceania (-0.39% and -0.21%); Latin America (+0.32% and +0.07%); Northern and Eastern Europe (+0.26% and +0.05%); Africa (+0.16% and +0.10%); North America (+0.12% and +0.32%); Eastern Mediterranean (-0.10% and +0.79%); Asia-Pacific (+0.07% and -0.06%); and the Indian subcontinent (+0.02% and +0.06%). There was a particularly marked reduction in current asthma symptom prevalence in English language countries (-0.51% and -0.09%). Similar patterns were observed for symptoms of severe asthma. However, the percentage of children reported to have had asthma at some time in their lives increased by 0.28% per year in the 13-14 year age group and by 0.18% per year in the 6-7 year age group. CONCLUSIONS: These findings indicate that international differences in asthma symptom prevalence have reduced, particularly in the 13-14 year age group, with decreases in prevalence in English speaking countries and Western Europe and increases in prevalence in regions where prevalence was previously low. Although there was little change in the overall prevalence of current wheeze, the percentage of children reported to have had asthma increased significantly, possibly reflecting greater awareness of this condition and/or changes in diagnostic practice. The increases in asthma symptom prevalence in Africa, Latin America and parts of Asia indicate that the global burden of asthma is continuing to rise, but the global prevalence differences are lessening.

Quadriceps strength predicts mortality in patients with moderate to severe Chronic Obstructive Pulmonary Disease

Abstract: Background: Prognosis in chronic obstructive pulmonary disease (COPD) is poorly predicted by indices of air flow obstruction, because other factors that reflect the systemic nature of the disease also influence prognosis. Objective: To test the hypothesis that a reduction in quadriceps maximal voluntary contraction force (QMVC) is a useful predictor of mortality in patients with COPD. Methods: A mortality questionnaire was sent to the primary care physician of 184 patients with COPD who had undergone quadriceps strength measurement over the past 5 years. QMVC was expressed as a percentage of the patient’s body mass index. The end point measured was death or lung transplantation, and median (range) follow-up was 38 (1–54) months. Results: Data were obtained for 162 patients (108 men and 54 women) with a mean (SD) percentage of forced expiratory volume in 1 s (FEV 1 ) predicted of 35.6 (16.2), giving a response rate of 88%. Transplant-free survival of the cohort was 93.5% at 1 year and 87.1% at 2 years. Cox regression models showed that the mortality risk increased with increasing age and with reducing QMVC. Only age (HR 1.72 (95% CI 1.14 to 2.6); p = 0.01) and QMVC (HR 0.91 (95% CI 0.83 to 0.99); p = 0.036) continued to be significant predictors of mortality when controlled for other variables in the multivariate analysis. Conclusion: QMVC is simple and provides more powerful prognostic information on COPD than that provided by age, body mass index and forced expiratory volume in 1 s.

Ascertainment of Cause-Specific Mortality in COPD -- Operations of the TORCH Clinical Endpoint Committee

Abstract: Background: TORCH (Towards a Revolution in COPD Health) is an international multicentre, randomised, placebo-controlled clinical trial of inhaled fluticasone propionate/salmeterol combination treatment and its monotherapy components for maintenance treatment of moderately to severely impaired patients with chronic obstructive pulmonary disease (COPD). The primary outcome is all-cause mortality. Cause-specific mortality and deaths related to COPD are additional outcome measures, but systematic methods for ascertainment of these outcomes have not previously been described. Methods: A Clinical Endpoint Committee (CEC) was tasked with categorising the cause of death and the relationship of deaths to COPD in a systematic, unbiased and independent manner. The key elements of the operation of the committee were the use of predefined principles of operation and definitions of cause of death and COPD-relatedness; the independent review of cases by all members with development of a consensus opinion; and a substantial infrastructure to collect medical information. Results: 911 deaths were reviewed and consensus was reached in all. Cause-specific mortality was: cardiovascular 27%, respiratory 35%, cancer 21%, other 10% and unknown 8%. 40% of deaths were definitely or probably related to COPD. Adjudications were identical in 83% of blindly re-adjudicated cases (κ = 0.80). COPD-relatedness was reproduced 84% of the time (κ = 0.73). The CEC adjudication was equivalent to the primary cause of death recorded by the site investigator in 52% of cases. Conclusion: A CEC can provide standardised, reliable and informative adjudication of COPD mortality that provides information which frequently differs from data collected from assessment by site investigators.

Time trends in allergic disorders in the UK

Abstract: Background: Allergic disorders are common in the UK. This study reviews recent UK time trends in the prevalence, morbidity and mortality for allergic disorders, excluding asthma. Methods: A trend analysis was performed over recent decades of national, representative or repeat surveys, primary care consultations, prescriptions, hospital admissions, and mortality. Results: Serial surveys showed that the prevalence of diagnosed allergic rhinitis and eczema in children have both trebled over the last three decades. While these long term trends were paralleled by the prevalence of disease symptoms, more recent symptom prevalence data suggest a decline. Similarly, GP consultation rates rose by 260% for hay fever and by 150% for eczema overall during the period 1971–91, but rates have stabilised over the past decade. Hospital admissions for eczema have been stable since 1995, and hospital admissions for allergic rhinitis have fallen to about 40% of their 1990 levels. Since 1990, admissions for anaphylaxis have increased by 700%, for food allergy by 500%, for urticaria by 100%, and for angio-oedema by 40%. Prescriptions issued for all types of allergy have increased since 1991. Conclusions: The prevalence and healthcare usage for eczema and hay fever have increased substantially over recent decades, but may now be stabilising or even falling. In contrast, admissions for some systemic allergic diseases have risen sharply in the last decade which may indicate a rising incidence of these conditions. Although changes in treatment and other healthcare factors may have contributed to these trends, there may also be a change in the aetiology of allergic disease in the UK.

Pathological features and inhaled corticosteroid response of eosinophilic and non-eosinophilic asthma

Abstract: Background: Non-eosinophilic asthma is a potentially important clinicopathological phenotype since there is evidence that it responds poorly to inhaled corticosteroid therapy. However, little is known about the underlying airway immunopathology and there are no data from placebo-controlled studies examining the effect of inhaled corticosteroids. Methods: Airway immunopathology was investigated using induced sputum, bronchial biopsies, bronchial wash and bronchoalveolar lavage in 12 patients with symptomatic eosinophilic asthma, 11 patients with non-eosinophilic asthma and 10 healthy controls. The patients with non-eosinophilic asthma and 6 different patients with eosinophilic asthma entered a randomised, double-blind, placebo-controlled crossover study in which the effects of inhaled mometasone 400 μg once daily for 8 weeks on airway responsiveness and asthma quality of life were investigated. Results: Patients with non-eosinophilic asthma had absence of eosinophils in the mucosa (median 4.4 cells/mm2 vs 23 cells/mm2 in eosinophilic asthma and 0 cells/mm2 in normal controls; p = 0.03) and normal subepithelial layer thickness (5.8 μm vs 10.3 μm in eosinophilic asthma and 5.1 μm in controls, p = 0.002). Non-eosinophilic and eosinophilic asthma groups had increased mast cell numbers in the airway smooth muscle compared with normal controls (9 vs 8 vs 0 cells/mm2, p = 0.016). Compared with placebo, 8 weeks of treatment with inhaled mometasone led to less improvement in methacholine PC20 (0.5 vs 5.5 doubling concentrations, 95% CI of difference 1.1 to 9.1; p = 0.018) and asthma quality of life (0.2 vs 1.0 points, 95% CI of difference 0.27 to 1.43; p = 0.008). Conclusions: Non-eosinophilic asthma represents a pathologically distinct disease phenotype which is characterised by the absence of airway eosinophilia, normal subepithelial layer thickness and a poor short-term response to treatment with inhaled corticosteroids.

Effect of CPAP on insulin resistance and HbA1c in men with obstructive sleep apnoea and type 2 diabetes

Abstract: BACKGROUND: The effects of continuous positive airway pressure (CPAP) for obstructive sleep apnoea (OSA) on insulin resistance are not clear. Trials have found conflicting results and no appropriate control groups have been used. METHODS: Forty-two men with known type 2 diabetes and newly diagnosed OSA (>10 dips/h in oxygen saturation of >4%) were randomised to receive therapeutic (n = 20) or placebo CPAP (n = 22) for 3 months. Baseline tests were performed and repeated after 3 months. The study was double blind. RESULTS: Results are expressed as mean (SD). CPAP improved the Epworth sleepiness score significantly more in the therapeutic group than in the placebo group (-6.6 (4.5) vs -2.6 (4.9), p = 0.01). The maintenance of wakefulness test improved significantly in the therapeutic group but not in the placebo group (+10.6 (13.9) vs -4.7 (11.8) min, p = 0.001). Glycaemic control and insulin resistance did not significantly change in either the therapeutic or placebo groups: HbA1c (-0.02 (1.5) vs +0.1 (0.7), p = 0.7, 95% CI -0.6% to +0.9%), euglycaemic clamp (M/I: +1.7 (14.1) vs -5.7 (14.8), p = 0.2, 95% CI -1.8 to +0.3 l/kg/min(1000)), HOMA-%S (-1.5 (2.3) vs -1.1 (1.8), p = 0.2, 95% CI -0.3% to +0.08%) and adiponectin (-1.1 (1.2) vs -1.1 (1.3), p = 0.2, 95% CI -0.7 to +0.6 microg/ml). Body mass index, bioimpedance and anthropometric measurements were unchanged. Hours of CPAP use per night were 3.6 (2.8) in the treatment group and 3.3 (3.0) in the placebo group (p = 0.8). There was no correlation between CPAP use and the measures of glycaemic control or insulin resistance. CONCLUSION: Therapeutic CPAP does not significantly improve measures of glycaemic control or insulin resistance in men with type 2 diabetes and OSA.

Exacerbations in cystic fibrosis · 1: Epidemiology and pathogenesis

Abstract: With the improving survival of patients with cystic fibrosis (CF), the clinical spectrum of this complex multisystem disease continues to evolve. One of the most important clinical events for patients with CF in the course of this disease is an acute pulmonary exacerbation. Clinical and microbial epidemiology studies of CF pulmonary exacerbations continue to provide important insight into the course, prognosis and complications of the disease. This review provides a summary of the pathophysiology, clinical epidemiology and microbial epidemiology of a CF pulmonary exacerbation.

External validity of randomised controlled trials in asthma: to whom do the results of the trials apply?

Abstract: Background: Asthma is a heterogeneous disease with a wide range of clinical phenotypes, not all of which may be encompassed in the subjects included in randomised controlled trials (RCTs). This makes it difficult for clinicians to know to what extent the evidence derived from RCTs applies to a given patient. Aim: To calculate the proportion of individuals with asthma who would have been eligible for the major asthma RCTs from the data of a random community survey of respiratory health. Methods: A postal survey was sent to 3500 randomly selected individuals aged 25–75 years. Respondents were invited to complete a detailed respiratory questionnaire and pulmonary function testing. Participants with current asthma were assessed against the eligibility criteria of the 17 major asthma RCTs cited in the Global Initiative for Asthma (GINA) guidelines. Findings: A total of 749 participants completed the full survey, of whom 179 had current asthma. A median 4% of participants with current asthma (range 0–36%) met the eligibility criteria for the included RCTs. A median 6% (range 0–43%) of participants with current asthma on treatment met the eligibility criteria. Interpretation: This study shows that the major asthma RCTs on which the GINA guidelines are based may have limited external validity as they have been performed on highly selected patient populations. Most of the participants with current asthma on treatment in the community would not have been eligible for these RCTs.

Innate immune activation in neutrophilic asthma and bronchiectasis

Abstract: Background: The role of the innate immune system in the pathogenesis of asthma is unclear. Activation of innate immune receptors in response to bacterial lipopolysaccharide, viral infection and particulate matter triggers a pre-programmed inflammatory response, which involves interleukin (IL)8 and neutrophil influx. The inflammatory response in asthma is heterogeneous. Aim: To test the hypothesis that innate immune activation may be a relevant inflammatory mechanism in neutrophilic asthma where IL8 levels are increased. Methods: Induced sputum was obtained from non-smoking adults with asthma (n = 49), healthy controls (n = 13) and a positive reference group with bronchiectasis (n = 9). Subjects with asthma were classified into inflammatory subtypes using induced sputum cell counts. Sputum was examined for mRNA expression of the innate immune receptors toll-like receptor (TLR)2, TLR4 and CD14, and inflammatory cytokines. A separate sputum portion was dispersed and the supernatant assayed for surfactant protein A, IL8, soluble CD14 and endotoxin. Results: Expression of innate immune receptors was increased in subjects with bronchiectasis and neutrophilic asthma compared with other asthma subtypes and controls. Increased expression of the receptors TLR2, TLR4 and CD14, as well as the pro-inflammatory cytokines IL8 and IL1β, was observed. Subjects with neutrophilic asthma had higher airway levels of endotoxin than the other groups studied. Conclusion: There is evidence of activation of the innate immune system in asthma which results in the production of pro-inflammatory cytokines and may contribute to the pathogenesis of neutrophilic asthma.

Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis

Abstract: Background: A sensitive and valid non-invasive marker of early cystic fibrosis (CF) lung disease is sought. The lung clearance index (LCI) from multiple-breath washout (MBW) is known to detect abnormal lung function more readily than spirometry in children and teenagers with CF, but its relationship to structural lung abnormalities is unknown. A study was undertaken to determine the agreements between LCI and spirometry, respectively, with structural lung disease as measured by high-resolution computed tomography (HRCT) in children and teenagers with CF. Methods: A retrospective study was performed in 44 consecutive patients with CF aged 5–19 years (mean 12 years). At an annual check-up inspiratory and expiratory HRCT scans, LCI and spirometric parameters (forced expiratory volume in 1 s (FEV1) and maximal expiratory flow when 75% of forced vital capacity was expired (FEF75)) were recorded. Abnormal structure was defined as a composite HRCT score of >5%, the presence of bronchiectasis or air trapping >30%. Abnormal lung function was defined as LCI above the predicted mean +1.96 residual standard deviations (RSD), or FEV1 or FEF75 below the predicted mean −1.96 RSD. Sensitivity/specificity assessments and correlation analyses were done. Results: The sensitivity to detect abnormal lung structure was 85–94% for LCI, 19–26% for FEV1 and 62–75% for FEF75. Specificity was 43–65% for LCI, 89–100% for FEV1 and 75–88% for FEF75. LCI correlated better with HRCT scores (Rs +0.85) than FEV1 (−0.62) or FEF75 (−0.66). Conclusions: LCI is a more sensitive indicator than FEV1 or FEF75 for detecting structural lung disease in CF, and a normal LCI almost excludes HRCT abnormalities. The finding of an abnormal LCI in some patients with normal HRCT scans suggests that LCI may be even more sensitive than HRCT scanning for detecting lung involvement in CF.

Isolation prevalence of pulmonary non-tuberculous mycobacteria in Ontario, 1997–2003

Abstract: Rationale: The prevalence of pulmonary non-tuberculous mycobacterial (NTM) infection is reportedly increasing. Objectives: To study the “isolation prevalence” of pulmonary NTM in Ontario, Canada, between 1997 and 2003, and the frequency of pulmonary NTM “disease.” Methods: In a retrospective cohort, we studied “isolation prevalence” by reviewing all positive NTM culture results from the Tuberculosis and Mycobacteriology Laboratory, Ministry of Health and Long-Term Care, in Toronto, from 1997 to 2003. This laboratory identifies at least 90% of NTM isolates in Ontario, Canada. Prevalence was compared between years using with a negative binomial model. To study the frequency of “disease” (defined by American Thoracic Society criteria), we reviewed records of patients who had an isolate in 2003 and had been assessed at our hospital. Measurements and Main Results: There were 22,247 pulmonary isolates from 10,231 patients. The “isolation prevalence” of all species (excluding Mycobacterium gordonae) was 9.1/100,000 in 1997 and rose to 14.1/100,000 by 2003 (p<0.0001), with an average annual increase of 8.4%. Similar increases were observed for individual species. Two hundred patients assessed at our institution were studied using American Thoracic Society criteria for “disease.” Microbiologic criteria were fulfilled by 37%. Of patients with adequate data, 74% fulfilled clinical criteria, 77% fulfilled radiologic criteria and 33% fulfilled all criteria. Conclusions: The “isolation prevalence” of pulmonary NTM has significantly and rapidly increased in Ontario, a sizeable proportion of patients likely have “disease.”

Diagnosis of lung cancer by the analysis of exhaled breath with a colorimetric sensor array

Abstract: Background: The pattern of volatile organic compounds (VOCs) in the exhaled breath of patients with lung cancer may be unique. New sensor systems that detect patterns of VOCs have been developed. One of these sensor systems, a colorimetric sensor array, has 36 spots composed of different chemically sensitive compounds impregnated on a disposable cartridge. The colours of these spots change based on the chemicals with which they come into contact. In this proof of principle study, the ability of this sensor system to detect a pattern of VOCs unique to lung cancer is assessed. Methods: Individuals with lung cancer, those with other lung diseases and healthy controls performed tidal breathing of room air for 12 min while exhaling into a device designed to draw their breath across a colorimetric sensor array. The colour changes that occurred for each individual were converted into a numerical vector. The vectors were analysed statistically, using a random forests technique, to determine whether lung cancer could be predicted from the responses of the sensor. Results: 143 individuals participated in the study: 49 with non-small cell lung cancer, 18 with chronic obstructive pulmonary disease 15 with idiopathic pulmonary fibrosis 20 with pulmonary arterial hypertension 20 with sarcoidosis and 21 controls. A prediction model was developed using observations from 70% of the subjects. This model was able to predict the presence of lung cancer in the remaining 30% of subjects with a sensitivity of 73.3% and a specificity of 72.4% (p=0.01). Conclusions: The unique chemical signature of the breath of patients with lung cancer can be detected with moderate accuracy by a colorimetric sensor array.

Biomass fuels are the probable risk factor for chronic obstructive pulmonary disease in rural South China

Abstract: Background: There is increasing evidence for a possible association between chronic obstructive pulmonary disease (COPD) and the use of biomass fuels for cooking and heating in developing countries. Data on the prevalence of COPD and objective measurements of indoor pollution from biomass fuel have not been widely available from China. A study was undertaken to investigate the prevalence of COPD in two study communities in Guangdong province in China and to measure the association between COPD and indoor biomass fuel air pollution. Methods: A cluster disproportional random sampling survey was performed in populations aged over 40 years in urban (Liwang) and rural (Yunyan) areas in Guangdong, China. Spirometry was performed in all subjects and a post-bronchodilator ratio of the forced expiratory volume in 1 s to forced vital capacity of Results: The overall prevalence of COPD in the two areas (Liwang and Yunyan) was 9.4%. The prevalence of COPD in both the whole population and a subpopulation of non-smoking women in rural Yunyan was significantly higher than in urban Liwang (12.0% vs 7.4%, and 7.2% vs 2.5%, respectively). The use of biomass fuel was higher in rural Yunyan than in urban Liwang (88.1% vs 0.7%). Univariate analysis showed a significant association between COPD and exposure to biomass fuel for cooking. Multivariate analysis showed a positive association between COPD and urban/rural area (surrogate for fuel type and local exhaust ventilation in kitchen) after adjustment for sex, age group, body mass index, education, occupational exposure, respiratory disease in family, smoking status, life quality and cough in childhood; similar results were found in non-smoking women. Pollutants measurements showed that concentrations of carbon monoxide, particulate matter with an aerodynamic diameter ⩽10 μm, sulphur dioxide and nitrogen dioxide in the kitchen during biomass fuel combustion were significantly higher than those during LPG combustion. Conclusions: Indoor pollutants from biomass fuels may be an important risk factor for COPD in rural South China.

Reduction in sputum neutrophil and eosinophil numbers by the PDE4 inhibitor roflumilast in patients with COPD.

Abstract: Background: Roflumilast is a targeted oral once-daily administered phosphodiesterase 4 (PDE4) inhibitor with clinical efficacy in chronic obstructive pulmonary disease (COPD). Results from in vitro studies with roflumilast indicate that it has anti-inflammatory properties that may be applicable for the treatment of COPD. Methods: In a crossover study, 38 patients with COPD (mean (SD) age 63.1 (7.0) years, post-bronchodilator forced expiratory volume in 1 s (FEV 1 ) 61.0 (12.6)% predicted) received 500 μg roflumilast or placebo once daily for 4 weeks. Induced sputum samples were collected before and after 2 and 4 weeks of treatment. Differential and absolute cell counts were determined in whole sputum samples. Markers of inflammation were determined in sputum supernatants and blood. Spirometry was performed weekly. Results: Roflumilast significantly reduced the absolute number of neutrophils and eosinophils/g sputum compared with placebo by 35.5% (95% CI 15.6% to 50.7%; p = 0.002) and 50.0% (95% CI 26.8% to 65.8%; p 0.05). Levels of soluble interleukin-8, neutrophil elastase, eosinophil cationic protein and α 2 -macroglobulin in sputum and the release of tumour necrosis factor α from blood cells were significantly reduced by roflumilast compared with placebo treatment (p 1 improved significantly during roflumilast compared with placebo treatment with a mean difference between treatments of 68.7 ml (95% CI 12.9 to 124.5; p = 0.018). Conclusion: PDE4 inhibition by roflumilast treatment for 4 weeks reduced the number of neutrophils and eosinophils, as well as soluble markers of neutrophilic and eosinophilic inflammatory activity in induced sputum samples of patients with COPD. This anti-inflammatory effect may in part explain the concomitant improvement in post-bronchodilator FEV 1 .

Effects of cannabis on pulmonary structure, function and symptoms

Abstract: Background: Cannabis is the most widely used illegal drug worldwide. Long term use of cannabis is known to cause chronic bronchitis and airflow obstruction, however the frequency of macroscopic emphysema, the dose-response relationship and the dose equivalence of cannabis with tobacco has not been determined. Methods: A convenience sample of adults from the Greater Wellington Region was recruited into four smoking groups; cannabis only, tobacco only, combined cannabis and tobacco and non-smokers of either substance. Their respiratory status was assessed using high resolution CT scanning, pulmonary function tests and a respiratory and smoking questionnaire. Associations between respiratory status and cannabis use were examined by analysis of covariance and logistic regression. Results: A total of 339 subjects were recruited into the four groups. A dose-response relationship was found between cannabis smoking and reduced FEV1/FVC and sGaw, and increased TLC. For measures of airflow obstruction, one cannabis joint had a similar effect to between 2.5 and 6 tobacco cigarettes. Cannabis smoking was associated with decreased lung density on HRCT scans. Macroscopic emphysema was detected in 1/75 (1.3%), 15/92 (16.3%), 17/91 (18.9%) and 0/81 subjects in the cannabis only, combined cannabis and tobacco, tobacco alone and non-smoking groups respectively. Conclusions: Smoking cannabis was associated with a dose-related impairment of large airways function resulting in airflow obstruction and hyperinflation. In contrast, cannabis smoking was seldom associated with macroscopic emphysema. The 1:2.5 to 6 dose equivalence between cannabis joints and tobacco cigarettes for adverse effects on lung function is of major public health significance.

Maternal food consumption during pregnancy and asthma, respiratory and atopic symptoms in 5‐year‐old children

Abstract: Background We have previously reported associations between maternal vitamin E, vitamin D and zinc intakes during pregnancy and asthma, wheeze and eczema in 5-year-old children In this report we investigate whether maternal intake of specific foods during pregnancy is associated with asthma, and allergic outcomes in the same children Methods A longitudinal birth cohort study was conducted among 1924 children born to women recruited during pregnancy Maternal diet during pregnancy was assessed by food frequency questionnaire (FFQ) Cohort children were followed up at 5 years by symptom questionnaire and FFQ Food groups of interest were fruit, vegetables, fruit juice, whole grain products, fish, dairy products and fat spreads Trends across outcome groups defined by level of food intake are presented Results 1253 children participated at 5 years, maternal FFQ data were available for 1212 No consistent associations were found between childhood outcomes and maternal intake of the analysed foods, except for apples and fish Maternal apple intake was beneficially associated with ever wheeze (OR highest vs lowest tertile 063; 95% CI 042-095), ever asthma (OR 054; 032-092) and doctor-confirmed asthma (OR 047; 027- 082) in the children Maternal fish consumption was beneficially associated with doctor-confirmed eczema (OR ≥1/week vs never 057; 035-092) Conclusion There was no evidence for associations between maternal intake of most foods during pregnancy, and asthma, respiratory and allergic outcomes in 5-year- old children, except for apples and fish Consumption of apples and fish during pregnancy may have a protective effect against the development of childhood asthma and allergic disease

Muscle fibre type shifting in the vastus lateralis of patients with COPD is associated with disease severity: a systematic review and meta-analysis

Abstract: Background: Skeletal muscle dysfunction is a common feature in chronic obstructive pulmonary disease (COPD) which is associated with intrinsic muscular abnormalities. One of the most consistently reported alterations is a shift from fibre type I to II in the vastus lateralis of these patients. Surprisingly, the relationship between this shift and the severity and phenotype of COPD remains unclear. A study was conducted to determine whether vastus lateralis muscle fibre type proportions are associated with COPD disease severity and to provide reference values for the proportions of fibre types in the vastus lateralis in COPD. Methods: A systematic review and a meta-analysis were conducted in which muscle fibre type data and markers of disease severity were collected from the literature. Results: The forced expiratory volume in 1 s (FEV 1 ), the ratio of FEV 1 to forced vital capacity (FVC) and body mass index were positively associated with the proportion of type I fibres in COPD. A proportion of 51% for vastus lateralis fibre type I and 13% for fibre type IIX were calculated from the combined data as normal values for patients with typical GOLD stage 3–4 COPD aged 60–70 years. Based on these reference values, a proportion of fibre type I 29% were defined as pathologically abnormal. Conclusions: This review sheds new light on the relationship between skeletal muscle abnormalities and important hallmarks of the disease in severe COPD, and identifies absence of data in GOLD stages 1–2. This review also provides reference values on fibre type composition for diagnostic purposes in COPD.

50 years of asthma: UK trends from 1955 to 2004

Abstract: Trends in asthma indicators from population surveys (prevalence) and routine statistics (primary care, prescriptions, hospital admissions and mortality) in the UK were reviewed from 1955 to 2004. The prevalence of asthma increased in children by 2 to 3-fold, but may have flattened or even fallen recently. Current trends in adult prevalence are flat. The prevalence of a life-time diagnosis of asthma increased in all age groups. The incidence of new asthma episodes presenting to general practitioners increased in all ages to a plateau in the mid 1990s and has declined since. During the 1990s, the annual prevalence of new cases of asthma and of treated asthma in general practice showed no major change. Hospital admissions increased from the early 1960s, more so in children, until the late 1980s and have fallen since. Asthma mortality showed two waves, a shorter and more intense one in the mid 1960s and a longer and less intense one in the late 1970s and early 1980s. The relative roles of diagnostic transfer, coding changes, medical care and epidemiological factors are discussed.

Pharmacy Asthma Care Program (PACP) improves outcomes for patients in the community

Abstract: Background: Despite national disease management plans, optimal asthma management remains a challenge in Australia. Community pharmacists are ideally placed to implement new strategies that aim to ensure asthma care meets current standards of best practice. The impact of the Pharmacy Asthma Care Program (PACP) on asthma control was assessed using a multi-site randomised intervention versus control repeated measures study design. Methods: Fifty Australian pharmacies were randomised into two groups: intervention pharmacies implemented the PACP (an ongoing cycle of assessment, goal setting, monitoring and review) to 191 patients over 6 months, while control pharmacies gave their usual care to 205 control patients. Both groups administered questionnaires and conducted spirometric testing at baseline and 6 months later. The main outcome measure was asthma severity/control status. Results: 186 of 205 control patients (91%) and 165 of 191 intervention patients (86%) completed the study. The intervention resulted in improved asthma control: patients receiving the intervention were 2.7 times more likely to improve from “severe” to “not severe” than control patients (OR 2.68, 95% CI 1.64 to 4.37; p Conclusions: A pharmacist-delivered asthma care programme based on national guidelines improves asthma control. The sustainability and implementation of the programme within the healthcare system remains to be investigated.

Protective effect of fruits, vegetables and the Mediterranean diet on asthma and allergies among children in Crete

Abstract: Introduction: Atopy is not uncommon among children living in rural Crete; but wheeze and rhinitis are rare. We examined whether this discrepancy could be attributed to a high consumption of fresh fruit and vegetables or adherence to a traditional Mediterranean diet. Methods: A cross-sectional survey was performed in 690 children aged 7-18 years in rural Crete. Parents completed a questionnaire on the child's respiratory and allergic symptoms, and a 58-item food frequency questionnaire. Adherence to a Mediterranean diet was measured through a scale on 12 dietary items. Children underwent skin prick tests with 10 common aeroallergens. Results: 80% of children ate fresh fruit (and 68% vegetables) at least twice a day. The intake of grapes, oranges, apples, and fresh tomatoes - the main local products in Crete - had no association with atopy but was protective for wheezing and rhinitis. High consumption of nuts was found to be inversely associated with wheezing (OR, 0.46; 95% CI, 0.20-0.98), whereas margarine increased the risk of both wheeze (OR, 2.19; 95% CI, 1.01-4.82) and allergic rhinitis (OR, 2.10; 95% CI, 1.31-3.37). A high level of adherence to the Mediterranean diet was protective for allergic rhinitis (OR, 0.34; 95% CI, 0.18-0.64) while a more modest protection was observed for wheezing and atopy. Conclusion: Our data suggest a beneficial effect of commonly consumed fruits, vegetables and nuts, and of a high adherence to a traditional Mediterranean diet during childhood on symptoms of asthma and rhinitis. Diet may explain the relative lack of allergic symptoms in this population.

Chronic Obstructive Pulmonary Disease in the Older Adult: What Defines Abnormal Lung Function?

Abstract: Background: The Global Initiative on Obstructive Lung Disease (GOLD) stages for chronic obstructive pulmonary disease (COPD) uses a fixed ratio of the post- bronchodilator forced expiratory volume in one second ( FEV1 )/ forced vital capacity (FVC) of 0.70 as a threshold. Since the FEV1/FVC ratio declines with age, using the fixed ratio to define COPD may "overdiagnose" COPD in older populations Objective: To determine morbidity and mortality among older adults whose FEV1/FVC is less than 0.70 but greater than the lower limit of normal (LLN). Methods: We classified the severity of COPD in 4,965 participants age 65 years and older in the Cardiovascular Health Study using these two methods and determined the age-adjusted proportion of the population that died or had a COPD-related hospitalization in up to 11 years of follow-up. Results: 1621(32.6%) subjects died and 935 (18.8%) had at least one COPD-related hospitalization during the follow-up period. People (n=1134) whose FEV1/FVC fell between the LLN and the fixed ratio had an increased adjusted risk of death (hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.1, 1.5) and COPD-related hospitalization (HR 2.6, 95% CI 2.0, 3.3) during follow- up compared to asymptomatic individuals with normal lung function. Conclusion: In this cohort, subjects classified as "normal" using the LLN but abnormal using the fixed ratio were more likely to die and to have a COPD-related hospitalization during follow-up. This suggests that a fixed FEV1/FVC < 0.70 may identify at-risk patients, even among older adults.

Temporal relationship between air pollutants and hospital admissions for chronic obstructive pulmonary disease in Hong Kong

Abstract: Aims: To assess any relationship between the levels of ambient air pollutants and hospital admissions for chronic obstructive pulmonary disease (COPD) in Hong Kong. Methods: A retrospective ecological study was undertaken. Data of daily emergency hospital admissions to 15 major hospitals in Hong Kong for COPD and indices of air pollutants (sulphur dioxide (SO 2 ), nitrogen dioxide (NO 2 ), ozone (O 3 ), particulates with an aerodynamic diameter of 10 ) and 2.5 μm (PM 2.5 )) and meteorological variables from January 2000 to December 2004 were obtained from several government departments. Analysis was performed using generalised additive models with Poisson distribution, adjusted for the effects of time trend, season, other cyclical factors, temperature and humidity. Autocorrelation and overdispersion were corrected. Results: Significant associations were found between hospital admissions for COPD with all five air pollutants. Relative risks for admission for every 10 μg/m 3 increase in SO 2 , NO 2 , O 3 , PM 10 and PM 2.5 were 1.007, 1.026, 1.034, 1.024 and 1.031, respectively, at a lag day ranging from lag 0 to cumulative lag 0–5. In a multipollutant model, O 3 , SO 2 and PM 2.5 were significantly associated with increased admissions for COPD. SO 2 , NO 2 and O 3 had a greater effect on COPD admissions in the cold season (December to March) than during the warm season. Conclusion: Ambient concentrations of air pollutants have an adverse effect on hospital admissions for COPD in Hong Kong, especially during the winter season. This might be due to indoor exposure to outdoor pollution through open windows as central heating is not required in the mild winter. Measures to improve air quality are urgently needed.

Ventilation heterogeneity is a major determinant of airway hyperresponsiveness in asthma, independent of airway inflammation

Abstract: Background: Airway hyperresponsiveness is the ability of airways to narrow excessively in response to inhaled stimuli and is a key feature of asthma. Airway inflammation and ventilation heterogeneity have been separately shown to be associated with airway hyperresponsiveness. A study was undertaken to establish whether ventilation heterogeneity is associated with airway hyperresponsiveness independently of airway inflammation in subjects with asthma and to determine the effect of inhaled corticosteroids on this relationship. Methods: Airway inflammation was measured in 40 subjects with asthma by exhaled nitric oxide, ventilation heterogeneity by multiple breath nitrogen washout and airway hyperresponsiveness by methacholine challenge. In 18 of these subjects with uncontrolled symptoms, measurements were repeated after 3 months of treatment with inhaled beclomethasone dipropionate. Results: At baseline, airway hyperresponsiveness was independently predicted by airway inflammation (partial r 2 = 0.20, p 2 = 0.39, p 2 = 0.64, p Conclusions: Baseline ventilation heterogeneity is a strong predictor of airway hyperresponsiveness, independent of airway inflammation in subjects with asthma. Its persistent relationship with airway hyperresponsiveness following anti-inflammatory treatment suggests that it is an important independent determinant of airway hyperresponsiveness. Normalisation of ventilation heterogeneity is therefore a potential goal of treatment that may lead to improved long-term outcomes.

Effect of an MMP-9/MMP-12 inhibitor on smoke-induced emphysema and airway remodelling in guinea pigs

Abstract: Background: Matrix metalloproteases (MMPs) are believed to be important in the pathogenesis of cigarette smoke-induced emphysema, but this hypothesis has only been proved in the mouse and its applicability to other species, particularly humans, is uncertain. The role of MMPs in smoke-induced small airway remodelling is unknown. Methods: The effects of a dual MMP-9/MMP-12 inhibitor, AZ11557272, on the development of anatomical and functional changes of chronic obstructive pulmonary disease (COPD) in guinea pigs exposed daily to cigarette smoke for up to 6 months were examined. Results: At all times, smoke-induced increases in lavage inflammatory cells, lavage desmosine (a marker of elastin breakdown) and serum tumour necrosis factor α (TNFα) were completely abolished by AZ11557272. At 6 months there was an increase in lung volumes and airspace size. AZ11557272 returned the pressure- volume curve to control levels, decreased smoke-induced increases in total lung capacity, residual volume and vital capacity by about 70%, and also reversed smoke-induced airspace enlargement by about 70%. There was a very strong correlation between surface to volume ratio and both lavage desmosine and serum TNFα levels. AZ11557272 protected against smoke-mediated increases in small airway wall thickness but did not prevent smoke-induced increases in mean pulmonary artery pressure. Conclusions: An MMP-9/MMP-12 inhibitor can substantially ameliorate morphological emphysema, small airway remodelling and the functional consequences of these lesions in a non-murine species. These findings strengthen the idea that MMPs are important mediators of the anatomical changes behind COPD in humans, and suggest that MMP-9 and MMP-12 may be potential intervention targets.

Lung clearance index is a sensitive, repeatable and practical measure of airways disease in adults with cystic fibrosis

Abstract: Background: Lung clearance index (LCI) is a sensitive marker of early lung disease in children but has not been assessed in adults. Measurement is hindered by the complexity of the equipment required. The aims of this study were to assess performance of a novel gas analyser (Innocor) and to use it as a clinical tool for the measurement of LCI in cystic fibrosis (CF). Methods: LCI was measured in 48 healthy adults, 12 healthy school-age children and 33 adults with CF by performing an inert gas washout from 0.2% sulfur hexafluoride (SF 6 ). SF 6 signal:noise ratio and 10–90% rise time of Innocor were compared with a mass spectrometer used in similar studies in children. Results: Compared with the mass spectrometer, Innocor had a superior signal:noise ratio but a slower rise time (150 ms vs 60 ms) which may limit its use in very young children. Mean (SD) LCI in healthy adults was significantly different from that in patients with CF: 6.7 (0.4) vs 13.1 (3.8), p Conclusions: Innocor can be adapted to measure LCI and affords a simpler alternative to a mass spectrometer. LCI is raised in adults with CF with normal spirometry, and may prove to be a more sensitive marker of the effects of treatment in this group.

The value of multiple tests of respiratory muscle strength

Abstract: Background: Respiratory muscle weakness is an important clinical problem. Tests of varying complexity and invasiveness are available to assess respiratory muscle strength. The relative precision of different tests in the detection of weakness is less clear, as is the value of multiple tests. Methods: The respiratory muscle function tests of clinical referrals who had multiple tests assessed in our laboratories over a 6-year period were analysed. Thresholds for weakness for each test were determined from published and in-house laboratory data. The patients were divided into three groups: those who had all relevant measurements of global inspiratory muscle strength (group A, n = 182), those with full assessment of diaphragm strength (group B, n = 264) and those for whom expiratory muscle strength was fully evaluated (group C, n = 60). The diagnostic outcome of each inspiratory, diaphragm and expiratory muscle test, both singly and in combination, was studied and the impact of using more than one test to detect weakness was calculated. Results: The clinical referrals were primarily for the evaluation of neuromuscular diseases and dyspnoea of unknown cause. A low maximal inspiratory mouth pressure (Pimax) was recorded in 40.1% of referrals in group A, while a low sniff nasal pressure (Sniff Pnasal) was recorded in 41.8% and a low sniff oesophageal pressure (Sniff Poes) in 37.9%. When assessing inspiratory strength with the combination of all three tests, 29.6% of patients had weakness. Using the two non-invasive tests (Pimax and Sniff Pnasal) in combination, a similar result was obtained (low in 32.4%). Combining Sniff Pdi (low in 68.2%) and Twitch Pdi (low in 67.4%) reduced the diagnoses of patients with diaphragm weakness to 55.3% in group B. 38.3% of the patients in group C had expiratory muscle weakness as measured by maximum expiratory pressure (Pemax) compared with 36.7% when weakness was diagnosed by cough gastric pressure (Pgas), and 28.3% when assessed by Twitch T10. Combining all three expiratory muscle tests reduced the number of patients diagnosed as having expiratory muscle weakness to 16.7%. Conclusion: The use of single tests such as Pimax, Pemax and other available individual tests of inspiratory, diaphragm and expiratory muscle strength tends to overdiagnose weakness. Combinations of tests increase diagnostic precision and, in the population studied, they reduced the diagnosis of inspiratory, specific diaphragm and expiratory muscle weakness by 19–56%. Measuring both Pimax and Sniff Pnasal resulted in a relative reduction of 19.2% of patients falsely diagnosed with inspiratory muscle weakness. The addition of Twitch Pdi to Sniff Pdi increased diagnostic precision by a smaller amount (18.9%). Having multiple tests of respiratory muscle function available both increases diagnostic precision and makes assessment possible in a range of clinical circumstances.

Characterisation of phenotypes based on severity of emphysema in chronic obstructive pulmonary disease

Abstract: Background: Airflow limitation in chronic obstructive pulmonary disease (COPD) is caused by a mixture of small airway disease and emphysema, the relative contributions of which may vary among patients. Phenotypes of COPD classified purely based on severity of emphysema are not well defined and may be different from classical phenotypes, pink puffers and blue bloaters. Methods: To characterize clinical phenotypes based on severity of emphysema, we recruited 274 subjects with COPD, excluding physician-diagnosed bronchial asthma. For all subjects, we conducted a detailed interview of disease history and symptoms, quality of life (QOL) measurement, blood sampling, pulmonary function tests before and after inhalation of salbutamol (0.4 mg), and high-resolution computed tomography. Results: Severity of emphysema visually evaluated varied widely even among subjects with the same stage of disease. No significant differences were noted among three groups of subjects classified by severity of emphysema in any of age, smoking history, chronic bronchitis symptoms, blood eosinophil count, serum IgE level or bronchodilator response. However, subjects with severe emphysema displayed significantly lower body-mass index (BMI) and poorer QOL scores, evaluated using St. George9s respiratory questionnaire (SGRQ), compared to subjects with no/mild emphysema (BMI: 21.2±0.5 vs. 23.5±0.3, respectively; SGRQ total score: 40±3 vs. 28±2, respectively; p<0.001 for both). These characteristics held true even if subjects with the same degree of airflow limitation were chosen. Conclusions: Severity of emphysema is widely varied even in the same stage of COPD, and chronic bronchitis symptoms are equally distributed irrespective of emphysema severity. The phenotype with emphysema in predominance has lower BMI and poorer health-related QOL.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: an under‐recognised spectrum of disease

Abstract: Aims and Methods: A review was undertaken of 19 patients diagnosed with diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) between 1992 and 2006. Results: Most patients were women (n = 15) and non-smokers (n = 16). Clinical presentation was either with symptomatic pulmonary disease (group 1; n = 9) or as an incidental finding during investigation for another disorder, most frequently malignant disease (group 2; n = 10). In group 1, cough and dyspnoea were the most frequent symptoms, with an average duration of 8.6 years before diagnosis. Both groups showed mainly stable disease without treatment, although one patient progressed to severe airflow obstruction and one was diagnosed at single lung transplantation. Mosaicism with nodule(s) was the typical pattern of DIPNECH on high-resolution computed tomography, but one case had normal imaging despite airflow obstruction. Lung function tests showed obstructive (n = 8), mixed (n = 3) or normal (n = 5, all group 2) physiology. Two patients underwent a bronchoalveolar lavage and showed a lymphocytosis (30%) with mild chronic bronchiolitis being seen in all biopsies. Tumourlets and associated typical carcinoids (n = 9) showed weak positivity for thyroid transcription factor-1. Three patients had atypical carcinoids, one with multiple endocrine neoplasia type 1 syndrome. Conclusions: DIPNECH is being increasingly recognised, probably because of an increase in the usage and accuracy of investigative imaging and increased awareness of the entity. Most cases remain stable over many years independent of the mode of presentation, although a few patients progress to severe airflow obstruction.

Randomised study of three non-surgical treatments in mild to moderate obstructive sleep apnoea

Abstract: Background: Patients with mild to moderate obstructive sleep apnoea (OSA) may be managed with different treatment options. This study compared the effectiveness of three commonly used non-surgical treatment modalities. Methods: Subjects with mild to moderate OSA were randomised to one of three treatment groups for 10 weeks: conservative measures (sleep hygiene) only, continuous positive airways pressure (CPAP) in addition to conservative measures or an oral appliance in addition to conservative measures. All overweight subjects were referred to a weight-reduction class. OSA was assessed by polysomnography. Blood pressure was recorded in the morning and evening in the sleep laboratory. Daytime sleepiness was assessed with the Epworth Sleepiness Scale. Health-related quality of life (HRQOL) was assessed with the 36-Item Short-Form Health Survey (SF-36) and Sleep Apnoea Quality of Life Index (SAQLI). Results: 101 subjects with a mean (SEM) apnoea–hypopnoea index (AHI) of 21.4 (1.1) were randomised to one of the three groups. The severity of sleep-disordered breathing was decreased in the CPAP and oral appliance groups compared with the conservative measures group, and the CPAP group was significantly better than the oral appliance group. Relief from sleepiness was significantly better in the CPAP group. CPAP was also better than the oral appliance or conservative measures in improving the “bodily pain” domain, and better than conservative measures in improving the “physical function” domain of SF-36. Both CPAP and the oral appliance were more effective than conservative measures in improving the SAQLI, although no difference was detected between the CPAP and oral appliance groups. CPAP and the oral appliance significantly lowered the morning diastolic blood pressure compared with baseline values, but there was no difference in the changes in blood pressure between the groups. There was also a linear relationship between the changes in AHI and body weight. Conclusion: CPAP produced the best improvement in terms of physiological, symptomatic and HRQOL measures, while the oral appliance was slightly less effective. Weight loss, if achieved, resulted in an improvement in sleep parameters, but weight control alone was not uniformly effective.

Early detection of cystic fibrosis lung disease: multiple-breath washout versus raised volume tests

Abstract: Background: Lung clearance index (LCI), a measure of ventilation inhomogeneity derived from the multiple-breath inert gas washout (MBW) technique, has been shown to detect abnormal lung function more readily than spirometry in preschool children with cystic fibrosis, but whether this holds true during infancy is unknown. Objectives: To compare the extent to which parameters derived from the MBW and the raised lung volume rapid thoraco–abdominal compression (RVRTC) techniques identify diminished airway function in infants with cystic fibrosis when compared with healthy controls. Methods: Measurements were performed during quiet sleep, with the tidal breathing MBW technique being performed before the forced expiratory manoeuvres. Results: Measurements were obtained in 39 infants with cystic fibrosis (mean (SD) age 41.4 (22.0) weeks) and 21 controls (37.0 (15.1) weeks). Infants with cystic fibrosis had a significantly higher respiratory rate (38 (10) vs 32 (5) bpm) and LCI (8.4 (1.5) vs 7.2 (0.3)), and significantly lower values for all forced expiratory flow-volume parameters compared with controls. Girls with cystic fibrosis had significantly lower forced expiratory volume (FEV 0.5 and FEF 25–75 ) than boys (mean (95% CI girls–boys): –1.2 (–2.1 to −0.3) for FEV 0.5 Z score; FEF 25–75 : –1.2 (–2.2 to −0.15)). When using both the MBW and RVRTC techniques, abnormalities were detected in 72% of the infants with cystic fibrosis, with abnormalities detected in 41% using both techniques and a further 15% by each of the two tests performed. Conclusions: These findings support the view that inflammatory and/or structural changes in the airways of children with cystic fibrosis start early in life, and have important implications regarding early detection and interventions. Monitoring of early lung disease and functional status in infants and young children with cystic fibrosis may be enhanced by using both MBW and the RVRTC.