Dp Johns

Airway inflammation, basement membrane thickening and bronchial hyperresponsiveness in asthma

Background: There are few data in asthma relating airway physiology, inflammation and remodelling and the relative effects of inhaled corticosteroid (ICS) treatment on these parameters. A study of the relationships between spirometric indices, airway inflammation, airway remodelling, and bronchial hyperreactivity (BHR) before and after treatment with high dose inhaled fluticasone propionate (FP 750 μg bd) was performed in a group of patients with relatively mild but symptomatic asthma. Methods: A double blind, randomised, placebo controlled, parallel group study of inhaled FP was performed in 35 asthmatic patients. Bronchoalveolar lavage (BAL) and airway biopsy studies were carried out at baseline and after 3 and 12 months of treatment. Twenty two normal healthy non-asthmatic subjects acted as controls. Results: BAL fluid eosinophils, mast cells, and epithelial cells were significantly higher in asthmatic patients than in controls at baseline (p<0.01). Subepithelial reticular basement membrane (rbm) thickness was variable, but overall was increased in asthmatic patients compared with controls (p<0.01). Multiple regression analysis explained 40% of the variability in BHR, 21% related to rbm thickness, 11% to BAL epithelial cells, and 8% to BAL eosinophils. The longitudinal data corroborated the cross sectional model. Forced expiratory volume in 1 second improved after 3 months of treatment with FP with no further improvement at 12 months. PD20 improved throughout the study. BAL inflammatory cells decreased following 3 months of treatment with no further improvement at 12 months (p<0.05 v placebo). Rbm thickness decreased in the FP group, but only after 12 months of treatment (mean change –1.9, 95% CI –3 to –0.7 μm; p<0.01 v baseline, p<0.05 v placebo). A third of the improvement in BHR with FP was associated with early changes in inflammation, but the more progressive and larger improvement was associated with the later improvement in airway remodelling. Conclusion: Physiology, airway inflammation and remodelling in asthma are interrelated and improve with ICS. Changes are not temporally concordant, with prolonged treatment necessary for maximal benefit in remodelling and PD20. Determining the appropriate dose of inhaled steroids only by reference to symptoms and lung function, as specified in current international guidelines, and even against indices of inflammation may be over simplistic. The results of this study support the need for early and long term intervention with ICS, even in patients with relatively mild asthma.

Biological dust exposure in the workplace is a risk factor for chronic obstructive pulmonary disease

Background: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Although the main risk factor is smoking, 15–19% of COPD even in smokers has been attributed to occupational exposures. The aim of this study was to investigate the association between occupational exposure and risk of COPD. Methods: Participants were part of a cross sectional study of risk factors for COPD. A total of 1232 completed a detailed respiratory questionnaire, spirometric testsing and measurement of gas transfer. Job histories were coded according to the International Standard Classification of Occupations. These codes were then used to establish occupational exposures using the ALOHA job exposure matrix. Results: The prevalence of emphysema was 2.4%, chronic obstructive bronchitis 1.8%, and COPD 3.4%. Subjects ever exposed to biological dusts had an increased risk of chronic obstructive bronchitis (OR 3.19; 95% CI 1.27 to 7.97), emphysema (OR 3.18; 95% CI 1.41 to 7.13), and COPD (OR 2.70, 95% CI 1.39 to 5.23). These risks were higher in women than in men. For biological dust, the risk of emphysema and COPD was also significantly increased in both the duration of exposure categories, again in women but not in men. No significant increased risks for COPD were found for mineral dust (OR 1.13; 95% CI 0.57 to 2.27) or gases/fumes (OR 1.63; 95% CI 0.83 to 3.22). Conclusion: In this general population sample of adults, occupational exposures to biological dusts were associated with an increased risk of COPD which was higher in women. Preventive strategies should be aimed at reducing exposure to these agents in the workplace.

The Interplay between the Effects of Lifetime Asthma, Smoking, and Atopy on Fixed Airflow Obstruction in Middle Age

RATIONALE The contribution by asthma to the development of fixed airflow obstruction (AO) and the nature of its effect combined with active smoking and atopy remain unclear. OBJECTIVES To investigate the prevalence and relative influence of lifetime asthma, active smoking, and atopy on fixed AO in middle age. METHODS The population-based Tasmanian Longitudinal Health Study cohort born in 1961 (n = 8,583) and studied with prebronchodilator spirometry in 1968 was retraced (n = 7,312) and resurveyed (n = 5,729 responses) from 2002 to 2005. A sample enriched for asthma and chronic bronchitis underwent a further questionnaire, pre- and post-bronchodilator spirometry (n = 1,389), skin prick testing, lung volumes, and diffusing capacity measurements. Prevalence estimates were reweighted for sampling fractions. Multiple linear and logistic regression were used to assess the relevant associations. MEASUREMENTS AND MAIN RESULTS Main effects and interactions between lifetime asthma, active smoking, and atopy as they relate to fixed AO were measured. The prevalence of fixed AO was 6.0% (95% confidence interval [CI], 4.5-7.5%). Its association with early-onset current clinical asthma was equivalent to a 33 pack-year history of smoking (odds ratio, 3.7; 95% CI, 1.5-9.3; P = 0.005), compared with a 24 pack-year history for late-onset current clinical asthma (odds ratio, 2.6; 95% CI, 1.03-6.5; P = 0.042). An interaction (multiplicative effect) was present between asthma and active smoking as it relates to the ratio of post-bronchodilator FEV(1)/FVC, but only among those with atopic sensitization. CONCLUSIONS Active smoking and current clinical asthma both contribute substantially to fixed AO in middle age, especially among those with atopy. The interaction between these factors provides another compelling reason for atopic individuals with current asthma who smoke to quit.

A mixed methods study to compare models of spirometry delivery in primary care for patients at risk of COPD

Background: To increase recognition of airflow obstruction in primary care, we compared two models of spirometry delivery in a target group at risk of chronic obstructive pulmonary disease (COPD). Methods: A 6 month qualitative/quantitative cluster randomised study in eight practices compared opportunistic spirometry by “visiting trained nurses” (TN) with optimised “usual care” (UC) from general practitioners (GPs) for smokers and ex-smokers, aged over 35 years. Outcomes were: spirometry uptake and quality, new diagnoses of COPD and GPs’ experiences of spirometry. Results: In the eligible target population, 531/904 (59%) patients underwent spirometry in the TN model and 87/1130 (8%) patients in the UC model (p<0.0001). ATS spirometry standards for acceptability and reproducibility were met by 76% and 44% of tests in the TN and UC models, respectively (p<0.0001). 125 (24%) patients tested with the TN model and 38 (44%) with the UC model reported a pre-existing respiratory diagnosis (p<0.0001). Three months after spirometry, when the ratio of forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) was <0.7 and no prior COPD diagnosis was reported, nine (8%) participants had a new doctor recorded COPD diagnosis in practices with the TN model and two (8%) participants in practices with the UC model. Mislabelling of participants with a diagnosis of COPD when FEV1/FVC was ⩾0.7 was present in both models prior to and after spirometry. GPs valued high quality spirometry and increased testing of patients at risk of COPD in the TN model. They identified limitations, including the need for better systematic follow-up of abnormal spirometry and support with interpretation, which may explain persisting underdiagnosis of COPD in practice records. Conclusions: Although opportunistic testing by visiting trained nurses substantially increased and improved spirometry performance compared with usual care, translating increased detection of airflow obstruction into diagnosis of COPD requires further development of the model. Trial registration number: Australian Clinical Trials Registry: registration No 12605000019606.

Childhood eczema and asthma incidence and persistence: A cohort study from childhood to middle age

BACKGROUND The association between eczema and asthma is well documented, but the temporal sequence of this association has not been closely examined. OBJECTIVES To examine the association between childhood eczema and asthma incidence from preadolescence to middle age, and between childhood eczema and asthma persisting to middle age. A further aim was to examine any effect modification by nonallergic childhood exposures on the association between childhood eczema and both childhood asthma and later life incident asthma. METHODS Data were gathered from the 1968, 1974, and 2004 surveys of the Tasmanian Longitudinal Health Study. Multivariable logistic regression examined the association between childhood eczema and childhood asthma. Cox regression examined the association between childhood eczema and asthma incidence in preadolescence, adolescence, and adult life. Binomial regression examined the association between childhood eczema and childhood asthma persisting to age 44 years. RESULTS Childhood eczema was significantly associated with childhood asthma and with incident asthma in preadolescence (hazard ratio [HR], 1.70; 95% CI, 1.05-2.75), adolescence (HR, 2.14; 95% CI, 1.33-3.46), and adult life (HR, 1.63; 95% CI, 1.28-2.09). Although childhood eczema was significantly associated with asthma persisting from childhood to middle age (relative risk, 1.54; 95% CI, 1.17-2.04), this association was no longer evident when adjusted for allergic rhinitis. CONCLUSION Childhood eczema increased the likelihood of childhood asthma, of new-onset asthma in later life and of asthma persisting into middle age.

Stability of the EasyOne ultrasonic spirometer for use in general practice.

Objective and background:  Spirometry is recommended for the diagnosis and management of chronic respiratory diseases in the community. Spirometer accuracy is critical, but few general practitioners meet the American Thoracic Society and European Respiratory Society (ATS/ERS) recommendation for daily calibration. The aim of this study was to assess the accuracy and stability of a portable ultrasonic spirometer (EasyOne) that the manufacturer claims does not require regular calibration.

Inter-relationships between airway inflammation, reticular basement membrane thickening and bronchial hyper-reactivity to methacholine in asthma; a systematic bronchoalveolar lavage and airway biopsy analysis

Background Asthma is accepted as a disease characterized by airway inflammation, with evidence that airway structural changes, or ‘remodelling’ occurs. There are few studies relating airway physiology, inflammation and remodelling, however. We have carried out a study of inter‐relationships between airway inflammation, airway remodelling, reticular basement membrane (RBM) thickening, and bronchial hyper‐reactivity (BHR), before and after high‐dose inhaled corticosteroid (fluticasone propionate 750 μg b.d.), in a group of relatively mild but symptomatic, steroid naïve asthma patients.

Adherence to Asthma Management Guidelines by Middle Aged Adults with Current Asthma

Background: With the increasing burden of asthma worldwide, much effort has been given to developing and updating management guidelines. Using data from the Tasmanian Longitudinal Health Study (TAHS), the adequacy of asthma management for middle-aged adults with asthma was investigated. Methods: Information about spirometry, medication history and current asthma status was collected by the most recent TAHS when participants were in their mid 40s. Only those who reported ever having asthma were eligible for analysis. Results: Of the 702 participants who reported ever having asthma, 50% had current asthma (n = 351) of whom 71% were categorised as having persistent asthma (n = 98 mild, n = 92 moderate, n = 58 severe). The majority (85.2%) of participants with current asthma had used some form of asthma medication in the past 12 months, but the proportion of the use of minimally adequate preventer medication was low (26%). Post-bronchodilator airflow obstruction increased progressively from mild to severe persistent asthma for those inadequately managed, but not for those on adequate therapy. Conclusion: Appropriate use of asthma medication by this middle-aged group of adults with current asthma was inadequate, especially for those with adult-onset moderate or severe persistent disease and without a family history of asthma. These results suggest that proper use of preventer medication could protect against the progressive decline in lung function associated with increasing severity. This has implications not just for poor quality of life, but also for the development of fixed airflow obstruction.

β2-adrenergic receptor polymorphisms are associated with asthma and COPD in adults

AbstractThe β2-adrenergic receptor (β2AR) is a transmembrane protein expressed by airway smooth muscle cells. In vitro studies have shown that polymorphisms at amino acid positions 16 and 27 alter receptor function. The aim of this study was to examine the associations between the β2AR polymorphisms and risks of asthma, chronic obstructive pulmonary disease (COPD) and respiratory symptoms in a sample of adults. Participants were part of a cross-sectional population-based study of risk factors for respiratory disease. A total of 1,090 Caucasian participants completed a detailed respiratory questionnaire, spirometry, methacholine challenge and measurement of gas transfer. Genotyping for β2AR polymorphisms at positions 16 and 27 was performed using the tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method. Haplotype frequencies for the two polymorphisms were estimated using the E-M algorithm. We found the Arg16 homozygotes had an increased risk of COPD (OR 5.13; 95% CI 1.40,18.8), asthma (2.44; 1.12,5.31) and symptoms of wheeze (1.84; 1.02,3.35). The Gln27 homozygotes had an increased risk of asthma (2.08; 1.05,4.13) and bronchial hyperreactivity (BHR) (1.92; 1.07,3.46). The Arg16/Gln27 haplotype was associated with asthma (1.63; 1.12,2.38) and COPD (2.91; 1.42,5.94). The Arg16/Gln27 β2AR haplotype is important in COPD, asthma and BHR, and may be associated with more severe respiratory symptoms in middle-aged and older adults.

National survey of spirometer ownership and usage in general practice in Australia

Objectives and background:  Despite the lack of data, it is believed that spirometry is underutilized in general practice. The aim of the present study was to determine the availability of spirometry and the level of spirometry training in general practice throughout Australia and compare with international data.