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Objective To assess the prevalence of combined pulmonary fibrosis and emphysema (CPFE) in systemic sclerosis (SSc) patients with interstitial lung disease (ILD) and the effect of CPFE on the pulmonary function tests used to evaluate the severity of SSc-related ILD and the likelihood of pulmonary hypertension (PH). Methods High-resolution computed tomography (HRCT) scans were obtained in 333 patients with SSc-related ILD and were evaluated for the presence of emphysema and the extent of ILD. The effects of emphysema on the associations between pulmonary function variables and the extent of SSc-related ILD as visualized on HRCT and echocardiographic evidence of PH were quantified. Results Emphysema was present in 41 (12.3%) of the 333 patients with SSc-related ILD, in 26 (19.7%) of 132 smokers, and in 15 (7.5%) of 201 lifelong nonsmokers. When the extent of fibrosis was taken into account, emphysema was associated with significant additional differences from the expected values for diffusing capacity for carbon monoxide (DL co) (average reduction of 24.1%; P < 0.0005), and the forced vital capacity (FVC)/DL co ratio (average increase of 34.8%; P < 0.0005) but not FVC. These effects were identical in smokers and nonsmokers. Multivariate analysis showed that the presence of emphysema had a greater effect than echocardiographically determined PH on the FVC/DL co ratio, regardless of whether it was analyzed as a continuous variable or using a threshold value of 1.6 or 2.0. Conclusion Among patients with SSc-related ILD, emphysema is sporadically present in nonsmokers and is associated with a low pack-year history in smokers. The confounding effect of CPFE on measures of gas exchange has major implications for the construction of screening algorithms for PH in patients with SSc-related ILD. [ABSTRACT FROM AUTHOR]

Background Although asthma is characterized by variable airways obstruction, most studies of asthma phenotypes are cross-sectional. The stability of phenotypes defined either by biomarkers or by physiological variables was assessed by repeated measures over 1 year in the Pan-European BIOAIR cohort of adult asthmatics. Methods A total of 169 patients, 93 with severe asthma ( SA) and 76 with mild-to-moderate asthma ( MA), were examined at six or more visits during 1 year. Asthma phenotype clusters were defined by physiological variables (lung function, reversibility and age of onset of the disease) or by biomarkers (eosinophils and neutrophils in induced sputum). Results After 1 year of follow-up, the allocation to clusters was changed in 23.6% of all asthma patients when defined by physiological phenotypes and, remarkably, in 42.3% of the patients when stratified according to sputum cellularity ( P = 0.034). In the SA cohort, 30% and 48.6% of the patients changed allocation according to physiological and biomarker clustering, respectively. Variability of phenotypes was not influenced by change in oral or inhaled corticosteroid dose, nor by the number of exacerbations. Lower stability of single and repeated measure was found for all evaluated biomarkers (eosinophils, neutrophils and Fe NO) in contrast to good stability of physiological variables ( FEV1), quality of life and asthma control. Conclusion Phenotypes determined by biomarkers are less stable than those defined by physiological variables, especially in severe asthmatics. The data also imply that definition of asthma phenotypes is improved by repeated measures to account for fluctuations in lung function, biomarkers and asthma control. [ABSTRACT FROM AUTHOR]

To cite this article: Contoli M, Bousquet J, Fabbri LM, Magnussen H, Rabe KF, Siafakas NM, Hamid Q, Kraft M. The small airways and distal lung compartment in asthma and COPD: a time for reappraisal. Allergy 2010; 65: 141–151. The involvement of small airways in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD) has been debated for a long time. However, a proper definition of small airway disease is still lacking, and neither a widely accepted biomarker nor a functional parameter to assess small airway abnormalities and to explore the effect of tested compounds on small airways is available. Aiming towards increased knowledge and consensus on this topic, this perspective paper intends to (i) strengthen awareness among the scientific community on the role of small airways in asthma and COPD; (ii) examine the pros and cons of some biological, functional and imaging parameters in the assessment of small airway abnormalities; and (iii) discuss the evidence for distal airway pharmacological targeting in asthma and COPD. [ABSTRACT FROM AUTHOR]

Background Near-fatal asthma (NFA) is characterized by severe asthma attacks usually requiring intensive care unit admission. This phenotype of asthma has been studied mainly in acute conditions. Methods The aim of our study was to compare the clinical, functional and inflammatory characteristics of NFA patients with mild to severe asthmatics in stable conditions. We recruited 155 asthmatic patients from five centres of the European Network for Understanding Mechanisms of Severe Asthma: 67 patients with mild-to-moderate asthma controlled by low/medium doses of inhaled corticosteroids; 64 with severe asthma that, despite treatment with high doses of inhaled corticosteroids, long-acting β2-agonists and for 1/3 also with regular oral corticosteroids, had at least one asthma exacerbation in the previous year; 24 with an NFA episode in the previous 5 years in the absence of inclusion criteria for the previous groups. All the patients were examined in stable conditions. Results NFA patients were taking less corticosteroids and were less compliant to prescribed asthma medications than the other two groups of patients. Lung function, blood gases, atopic status, sputum and blood inflammatory cell count of NFA patients were similar to mild-to-moderate, but not severe, asthmatic patients. Conclusions In stable conditions patients with an NFA attack in the previous 5 years cannot be distinguished from patients with mild-to-moderate asthma, while they are different from severe asthmatics both in terms of lung function and of airway inflammation. The risk factor that characterizes this group of patients is reduced usage of prophylactic corticosteroids. [ABSTRACT FROM AUTHOR]

Background Expired breath condensate (EBC) has never been used to explore the level of oxidative stress in idiopathic pulmonary fibrosis (IPF). Therefore, the aim of this study was to measure the levels of H2O2 and 8-isoprostane, as biomarkers of oxidative stress, in the EBC of patients with IPF. Materials and methods We investigated 16 patients with IPF and 15 healthy subjects as the control group. The levels of H2O2 and 8-isoprostane were measured in the EBC of all subjects and were compared between the IPF and control groups. In patients with IPF, H2O2 and 8-isoprostane were further correlated with pulmonary function tests (PFTs), the resting pO2 and the differential cell count from the bronchoalveolar lavage fluid (BALF). Results The mean (95%CI) concentration of H2O2 was increased in the patients with IPF compared with the normal subjects (0·36, 0·24–0·47 µM vs. 0·16, 0·10–0·23 µM, P = 0·003) . The mean (95%CI) concentration of 8-isoprostane was also increased in the patients with IPF compared with the controls (74, 38–110 pg mL−1 vs. 33, 28–39 pg mL−1, P = 0·02). In the patients with IPF, the diffusing capacity of the lung for carbon monoxide was negatively correlated with the levels of H2O2 in EBC ( P = 0·03, r = −0·58). No other correlation was found between the oxidative stress markers in the EBC and PFT values, pO2 or BALF cell count. Conclusions Our data suggest that H2O2 and 8-isoprostane are increased in the EBC of patients with IPF. H2O2 may be correlated with the severity of the disease in IPF. [ABSTRACT FROM AUTHOR]

Severe persistent asthma (SPA) and chronic obstructive pulmonary disease (COPD) are both associated with non-reversible airflow limitation and airway neutrophilia. To compare inflammatory cell profiles and T lymphocyte subsets between SPA and COPD patients with similar severity of airflow limitation. Sputum induction and lung function tests were performed in 15 COPD patients aged (mean±SD) 68±8 years, ex-smokers, mean forced expiratory volume in 1 s (FEV1) 45% of predicted (%pred) and 13 SPA aged 55±10 years, non-smokers, mean FEV1 49%pred. All patients were on inhaled steroid treatment. Eight asthmatics exhibited irreversible airflow limitation. Differential cell count, metachromatic cell count and double immunocytochemistry for the analysis of T lymphocyte subsets were performed on sputum slides. COPD patients had increased sputum neutrophils in comparison with SPA ( P<0.03), but similar to SPA with fixed obstruction. In COPD sputum neutrophils negatively correlated with the lung transfer factor for carbon monoxide ( KCO) ( r=−0.462, P=0.04). SPA showed significantly increased eosinophils and metachromatic cells vs. COPD patients ( P<0.04, P<0.007, respectively). Increased CD4/CD8 and decreased CD4-IFN-γ/CD4-IL4+ cell ratio ( P<0.001) were found in SPA vs. COPD. In SPA, CD4/CD8+ cell ratio correlated with sputum eosinophils ( r=0.567, P=0.04). In spite of treatment with inhaled steroids, SPA and COPD exhibit distinct sputum inflammatory cell patterns, although SPA with fixed airflow limitation and COPD patients have similar numbers of neutrophils. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic interstitial pneumonia limited to the lung and characterized by a fibroproliferative response with only minor signs of inflammation, which almost always causes rapid fibrotic destruction of the lung. In this study, we investigated genomic instability in IPF, using microsatellite DNA analysis, aiming to detect any specific genetic alterations for this disease. We used 40 highly polymorphic microsatellite DNA markers, in multiplex PCR assays, to examine 52 sputum specimens from IPF patients versus correspondent venous blood. Loss of heterozygosity (LOH) was found in 20 (38.5%) patients in at least one locus. These alterations were found on markers previously associated with lung cancer located on 1p34.3, 3p21.32-p21.1, 5q32-q33.1, 9p21 and 17p13.1 where MYCL1, FHIT, SPARC, p16(Ink4) and TP53 genes have been mapped respectively. These data provide new insights into IPF pathogenesis and a new perspective for its correlation with lung cancer.