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This review is the summary of a workshop on the role of distal airways in chronic obstructive pulmonary disease (COPD), which took place in 2009 in Vence, France. The evidence showing inflammation and remodelling in distal airways and the possible involvement of these in the pathobiology, physiology, clinical manifestations and natural history of COPD were examined. The usefulness and limitations of physiological tests and imaging techniques for assessing distal airways abnormalities were evaluated. Ex vivo studies in isolated lungs and invasive measurements of airway resistance in living individuals have revealed that distal airways represent the main site of airflow limitation in COPD. Structural changes in small conducting airways, including increased wall thickness and obstruction by muco-inflammatory exudates, and emphysema (resulting in premature airway closure), were important determinants of airflow limitation. Infiltration of small conducting airways by phagocytes (macrophages and neutrophils), dendritic cells and T and B lymphocytes increased with airflow limitation. Distal airways abnormalities were associated with patient-related outcomes (e.g. dyspnoea and reduced health-related quality of life) and with the natural history of the disease, as reflected by lung function decline and mortality. These data provide a clear rationale for targeting distal airways in COPD.

The present review is the summary of an expert workshop that took place in Vence (France) in 2007 on the role of distal airways in asthma. The evidence showing inflammation and remodelling in distal airways, and their possible involvement in asthma control and natural history, was reviewed. The usefulness and limitations of various techniques used for assessing distal airways were also evaluated, including pulmonary function tests and imaging. Finally, the available data studying the benefit of treatment better targeting distal airways in asthma was examined. It was concluded that both proximal and distal airways were involved in asthma and that distal airways were the major determinant of airflow obstruction. Inflammation in distal airways appeared more intense in severe and uncontrolled asthma. Distal airways were poorly attained by conventional aerosol of asthma medications owing to their granulometry, being composed of 3–5 µm particles. Both proximal and distal airways might be targeted either by delivering medications systemically or by aerosol of extra-fine particles. Extra-fine aerosols of long-acting β-agonists, inhaled corticosteroids or inhaled corticosteroid/long-acting β-agonist combinations have been shown in short-term studies to be not inferior to non-extra-fine aerosols of comparators. However, available studies have not yet demonstrated that extra-fine inhaled medications offer increased benefit compared with usual aerosols in asthmatic patients.

Objectives: Lumacaftor-ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) modulator known to improve clinical status in people with cystic fibrosis (CF). The aim of this study was to assess lung structural changes after 1 year of lumacaftor-ivacaftor treatment and to use unsupervised machine learning to identify morphological phenotypes of lung disease that are associated with response to lumacaftor-ivacaftor., Methods: Adolescents and adults with CF from a French multicentre real-world prospective observational study evaluating the first year of treatment with lumacaftor-ivacaftor were included if they had pre-therapeutic and follow-up chest computed tomography (CT) scans available. CT scans were visually scored using a modified Bhalla score. A k-means clustering method was performed based on 120 radiomics features extracted from unenhanced pre-therapeutic chest CT scans., Results: In total, 283 patients were included. The Bhalla score significantly decreased after 1 year of lumacaftor-ivacaftor (-1.40±1.53 points compared with pre-therapeutic CT, p<0.001). This finding was related to a significant decrease in mucus plugging (-0.58±0.88 points, p<0.001), bronchial wall thickening (-0.35±0.62 points, p<0.001) and parenchymal consolidations (-0.24±0.52 points, p<0.001). Cluster analysis identified three morphological clusters. Patients from cluster C were more likely to experience an increase in per cent predicted forced expiratory volume in 1 s (FEV 1 % pred) ≥5% under lumacaftor-ivacaftor than those in the other clusters (54% of responders versus 32% and 33%; p=0.02)., Conclusion: 1-year treatment with lumacaftor-ivacaftor was associated with a significant visual improvement of bronchial disease on chest CT. Radiomics features on pre-therapeutic CT scans may help to predict lung function response under lumacaftor-ivacaftor., Competing Interests: Conflict of interest: A. Campredon has nothing to disclose. Conflict of interest: E. Battistella has nothing to disclose. Conflict of interest: C. Martin reports lecture payments or honoraria from Chiesi and Zambon, outside the submitted work. Conflict of interest: I. Durieu has nothing to disclose. Conflict of interest: L. Mely has nothing to disclose. Conflict of interest: C. Marguet reports consulting fees from Gleamer; lecture payments or honoraria from Vertex, Viatis and Zambon; support for attending meetings and/or travel from Zambon; and participation on a Data Safety Monitoring Board or Advisory Board for Zambon and Viatis; outside the submitted work. Conflict of interest: C. Belleguic has nothing to disclose. Conflict of interest: M. Murris-Espin has nothing to disclose. Conflict of interest: R. Chiron has nothing to disclose. Conflict of interest: A. Fanton has nothing to disclose. Conflict of interest: S. Bui reports payment for expert testimony for inhaled antibiotics for Zambon, outside the submitted work. Conflict of interest: M. Reynaud-Gaubert has nothing to disclose. Conflict of interest: P. Reix has nothing to disclose. Conflict of interest: T-N. Hoang-Thi has nothing to disclose. Conflict of interest: M. Vakalopoulou has nothing to disclose. Conflict of interest: M-P. Revel has nothing to disclose. Conflict of interest: J. Da Silva has nothing to disclose. Conflict of interest: P-R. Burgel reports grants or contracts from Vertex and GSK; consulting fees from AstraZeneca, Chiesi, GSK, Insmed, Vertex and Zambon; and lecture payments or honoraria from Pfizer and Novartis; outside the submitted work. Conflict of interest: G. Chassagnon reports lecture payments or honoraria from Chiesi, outside the submitted work., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Mild-to-moderate haemoptysis (m-mH) is common in patients with cystic fibrosis but the risk of subsequent massive haemoptysis (MH) is not known. Allergic bronchopulmonary aspergillosis and diabetes were significant predictors of MH subsequent to m-mH. https://bit.ly/30093Hw., Competing Interests: Conflict of interest: G. Pavaut has nothing to disclose. Conflict of interest: M. Kyheng has nothing to disclose. Conflict of interest: O. Le Rouzic reports personal fees and nonfinancial support from AstraZeneca, Boehringer Ingelheim, Chiesi, Lilly and Novartis, and nonfinancial support from GlaxoSmithKline, MundiPharma, Pfizer, Teva, the Santelys Association, Vertex and Vitalaire, outside the submitted work. Conflict of interest: T. Perez reports nonfinancial support for clinical studies in cystic fibrosis from Physioassist and Antadir outside the submitted work. Conflict of interest: B. Wallaert reports personal fees and nonfinancial support from Roche and Boehringer Ingelheim, and nonfinancial support from Vitalaire, outside the submitted work. Conflict of interest: A. Prevotat has nothing to disclose., (Copyright ©ERS 2020.)

Options to achieve oral corticosteroid (OCS)-sparing have been triggering increasing interest since the 1970s because of the side-effects of OCSs, and this has now become achievable with biologics. The Société de Pneumologie de Langue Française workshop on OCSs aimed to conduct a comprehensive review of the basics for OCS use in asthma and issue key research questions. Pharmacology and definition of regular use were reviewed by the first working group (WG1). WG2 examined whether regular OCS use is associated with T2 endotype. WG3 reported on the specificities of the paediatric area. Key "research statement proposals" were suggested by WG4. It was found that the benefits of regular OCS use in asthma outside episodes of exacerbations are poorly supported by the existing evidence. However, complete OCS elimination couldn't be achieved in any available studies for all patients and the panel felt that it was too early to conclude that regular OCS use could be declared criminal. Repeated or prolonged need for OCS beyond 1 g·year -1 should indicate the need for referral to secondary/tertiary care. A strategic sequential plan aiming at reducing overall exposure to OCS in severe asthma was then held as a conclusion of the workshop., Competing Interests: Conflict of interest: A. Bourdin reports institutional fees for board membership from AstraZeneca, Novartis, GSK, Boehringer Ingelheim, Chiesi, Actelion, Pfizer and Teva, outside the submitted work. Conflict of interest: I. Adcock reports grants from EU-IMI, during the conduct of the study. Conflict of interest: P. Berger reports non-financial support from AstraZeneca, during the conduct of the study; personal fees and non-financial support from AstraZeneca, Sanofi, Circassia and Menarini grants, personal fees and non-financial support from Boehringer Ingelheim, and grants and personal fees from Novartis, outside the submitted work. Conflict of interest: P. Bonniaud reports personal fees and other from Roche, Boehringer, Novartis, personal fees from TEVA and AstraZeneca, and other from Chiesi and Stallergene, outside the submitted work. Conflict of interest: P. Chanson has nothing to disclose. Conflict of interest: C. Chenivesse reports grants and personal fees from AstraZeneca and Novartis, and personal fees from AIR LIQUIDE, ALK Abello, Boehringher Ingelheim, Chiesi, GSK, Sanofi and Teva, outside the submitted work. Conflict of interest: J. de Blic reports institutional fees for board membership from GSK, Boehringer Ingelheim, AstraZeneca, Novartis, Chiesi and Stallergenes, outside the submitted work. Conflict of interest: A. Deschildre reports personal fees from Novartis, TEVA, Stallergenes Greer, AImmune, Zambon, personal fees and other from ALK, GSK, Chiesi, AstraZeneca and DBV technologies, outside the submitted work. Conflict of interest: P. Devillier reports personal fees and non-financial support from AstraZeneca and Boehringer Ingelheim, and personal fees from Chiesi, GlaxoSmithKline, Novartis and Sanofi, outside the submitted work. Conflict of interest: G. Devouassoux reports personal fees from GSK, Astra Zeneca and Novartis, during the conduct of the study. Conflict of interest: A. Didier reports institutional fees for board membership from AstraZeneca, Novartis, GSK, Boehringer Ingelheim, Chiesi and Menarini, outside the submitted work. Conflict of interest: G. Garcia reports institutional fees for board membership from AstraZeneca, Novartis, GSK, Boehringer Ingelheim, Chiesi, Actelio, Pfizer and Teva, outside the submitted work. Conflict of interest: A. Magnan has nothing to disclose. Conflict of interest: Y. Martinat reports institutional fees for board membership from AstraZeneca, Novartis, GSK, Boehringer Ingelheim, Chiesi, Actelio, Pfizer and Teva, outside the submitted work. Conflict of interest: T. Perez reports institutional fees for board membership from Novartis, GSK, Boehringer Ingelheim and Chiesi, grants from AstraZeneca, and fees for travel from Chiesi, AstraZeneca, and Boehringer Ingelheim, outside the submitted work. Conflict of interest: N. Roche reports grants and personal fees from Boehringer Ingelheim, Novartis and Pfizer, and personal fees from Teva, GSK, AstraZeneca, Chiesi, Mundipharma, Sanofi, Sandoz, 3M, Zambon and Trudell, outside the submitted work. Conflict of interest: C. Taillé reports personal fees, non-financial support and other from AstraZeneca and from Novartis, grants, personal fees, non-financial support and other from GSK and Sanofi, and personal fees from Teva, during the conduct of the study. Conflict of interest: P. Val has nothing to disclose. Conflict of interest: P. Chanez reports grants and personal fees from Almirall, Boehringer Ingelheim, ALK, GSK, AstraZeneca, Novartis, Teva and Chiesi, and grants from AMU, outside the submitted work., (Copyright ©ERS 2020.)

Background: The prevalence of Achromobacter xylosoxidans lung isolation in cystic fibrosis (CF) patients has increased, but the impact on lung function is controversial. The aim of this study was to evaluate the long-term effects of A. xylosoxidans isolation on respiratory function of adult patients with CF in the first 3 years after identification of A. xylosoxidans isolation., Methods: This was a case-control retrospective study performed at a single CF centre in Lille, France. Data for 36 patients with CF who had at least one sputum culture positive for A. xylosoxidans ( Ax+ ) were evaluated and compared with control CF patients uninfected by A. xylosoxidans ( Ax- ). Respiratory function and exacerbation frequency were evaluated between 1 year prior to and 3 years after A. xylosoxidans isolation., Results: Compared with the Ax - group, the Ax+ group had a lower forced expiratory volume in 1 s (FEV 1 ) at baseline (median (interquartile range): 55.2% (50.6-59.8%) versus 73.8% (67.2-80.4%); p=0.005), a greater decline in FEV 1 (±se) in the first year after A. xylosoxidans identification (-153.6±16.1 mL·year -1 versus -63.8±18.5 mL·year -1 ; p=0.0003), and more exacerbations in the first 3 years after A. xylosoxidans identification (9 (7-12) versus 7 (5-10); p=0.03). Ax+ patients co-colonised with Pseudomonas aeruginosa (n=27, 75%) had a greater FEV 1 decline (p=0.003) and more exacerbations in the year after A. xylosoxidans identification (p=0.037) compared with patients colonised with A. xylosoxidans alone. Patients with chronic A. xylosoxidans isolation (n=23, 64%) had more exacerbations than intermittently colonised patients in the 3 years after A. xylosoxidans identification (p=0.012)., Conclusion: A. xylosoxidans isolation is associated with a decline in respiratory function in patients with CF. Chronic A. xylosoxidans isolation and P. aeruginosa co-isolation may be markers of more severe respiratory disease in Ax + patients., Competing Interests: Conflict of interest: M. Tetart has nothing to disclose. Conflict of interest: F. Wallet has nothing to disclose. Conflict of interest: M. Kyheng has nothing to disclose. Conflict of interest: S. Leroy has nothing to disclose. Conflict of interest: T. Perez reports being the principal investigator of a clinical study evaluating a device for chest clearance in cystic fibrosis (Simeox, PhysioAssist). Conflict of interest: O. Le Rouzic reports personal fees and nonfinancial support from AstraZeneca, Boehringer Ingelheim, Chiesi, Lilly and Novartis, and nonfinancial support from GlaxoSmithKline, MundiPharma, Pfizer, Teva, the Santelys Association, Vertex and Vitalaire, outside the submitted work. Conflict of interest: B. Wallaert reports personal fees from Roche and Boehringer Ingelheim, outside the submitted work. Conflict of interest: A. Prevotat reports personal fees from Vertex and GSK, and congress invitations from Teva and Novartis, outside the submitted work., (Copyright ©ERS 2019.)

Chronic obstructive pulmonary disease (COPD) is characterised by nonreversible proximal bronchial obstruction leading to major respiratory disability. However, patient phenotypes better capture the heterogeneously reported complaints and symptoms of COPD. Recent studies provided evidence that classical bronchial obstruction does not properly reflect respiratory disability, and symptoms now form the new paradigm for assessment of disease severity and guidance of therapeutic strategies. The aim of this review was to explore pathways addressing COPD pathogenesis beyond proximal bronchial obstruction and to highlight innovative and promising tools for phenotyping and bedside assessment. Distal small airways imaging allows quantitative characterisation of emphysema and functional air trapping. Micro-computed tomography and parametric response mapping suggest small airways disease precedes emphysema destruction. Small airways can be assessed functionally using nitrogen washout, probing ventilation at conductive or acinar levels, and forced oscillation technique. These tests may better correlate with respiratory symptoms and may well capture bronchodilation effects beyond proximal obstruction.Knowledge of inflammation-based processes has not provided well-identified targets so far, and eosinophils probably play a minor role. Adaptative immunity or specific small airways secretory protein may provide new therapeutic targets. Pulmonary vasculature is involved in emphysema through capillary loss, microvascular lesions or hypoxia-induced remodelling, thereby impacting respiratory disability., Competing Interests: Conflict of interest: T. Capron has nothing to disclose. Conflict of interest: A. Bourdin reports personal fees from Novartis, Sanofi, Genentech and Chiesi Farma, and grants and personal fees from GSK, AstraZeneca and Boeringher Ingelheim, outside the submitted work. Conflict of interest: T. Perez reports personal fees from Novartis, Chiesi and Boehringer Ingelheim, and grants from Astra Zeneca, outside the submitted work. Conflict of interest: P. Chanez reports grants and personal fees from ALK, Almirall, Boehringer Ingelheim, GSK, AstraZeneca, Novartis, TEVA and Chiesi, and grants from AMU, outside the submitted work., (Copyright ©ERS 2019.)

Screening is important to determine whether patients with systemic sclerosis (SSc) have pulmonary hypertension because earlier pulmonary hypertension treatment can improve survival in these patients. Although decreased transfer factor of the lung for carbon monoxide ( T LCO ) is currently considered the best pulmonary function test for screening for pulmonary hypertension in SSc, small series have suggested that partitioning T LCO into membrane conductance (diffusing capacity) for carbon monoxide ( D MCO ) and alveolar capillary blood volume ( V C ) through combined measurement of T LCO and transfer factor of the lung for nitric oxide ( T LNO ) is more effective to identify pulmonary hypertension in SSc patients compared with T LCO alone. Here, the objective was to determine whether combined T LCO - T LNO partitioned with recently refined equations could more accurately detect pulmonary hypertension than T LCO alone in SSc.For that purpose, 572 unselected consecutive SSc patients were retrospectively recruited in seven French centres.Pulmonary hypertension was diagnosed with right heart catheterisation in 58 patients. T LCO , T LNO and V C were all lower in SSc patients with pulmonary hypertension than in SSc patients without pulmonary hypertension. The area under the receiver operating characteristic curve for the presence of pulmonary hypertension was equivalent for T LCO (0.82, 95% CI 0.79-0.85) and T LNO (0.80, 95% CI 0.76-0.83), but lower for V C (0.75, 95% CI 0.71-0.78) and D MCO (0.66, 95% CI 0.62-0.70).Compared with T LCO alone, combined T LCO - T LNO does not add capability to detect pulmonary hypertension in unselected SSc patients., Competing Interests: Conflict of interest: None declared., (Copyright ©ERS 2017.)

Dyspnoea is a prominent symptom of chronic obstructive pulmonary disease (COPD). Recent multidimensional dyspnoea questionnaires like the Multidimensional Dyspnea Profile (MDP) individualise the sensory and affective dimensions of dyspnoea. We tested the MDP in COPD outpatients based on the hypothesis that the importance of the affective dimension of dyspnoea would vary according to clinical characteristics.A multicentre, prospective, observational, real-life study was conducted in 276 patients. MDP data were compared across various categories of patients (modified Medical Research Council (mMRC) dyspnoea score, COPD Assessment Test (CAT) score, Global Initiative for Chronic Obstructive Lung Disease (GOLD) airflow obstruction categories, GOLD "ABCD" categories, and Hospital Anxiety and Depression Scale (HADS)). Univariate and multivariate regressions were conducted to explore factors influencing the affective dimension of dyspnoea. Cluster analysis was conducted to create homogeneous patient profiles.The MDP identified a more marked affective dimension of dyspnoea with more severe mMRC, CAT, 12-item Short-Form Health Survey mental component, airflow obstruction and HADS. Multivariate analysis identified airflow obstruction, depressive symptoms and physical activity as determinants of the affective dimension of dyspnoea. Patients clustered into an "elderly, ex-smoker, severe disease, no rehabilitation" group exhibited the most marked affective dimension of dyspnoea.An affective/emotional dimension of dyspnoea can be identified in routine clinical practice. It can contribute to the phenotypic description of patients. Studies are needed to determine whether targeted therapeutic interventions can be designed and whether they are useful., (Copyright ©ERS 2016.)

A short, easy-to-use health status questionnaire is needed in the multidimensional assessment of chronic obstructive pulmonary disease (COPD) in routine practice. The performance of the eight-item COPD assessment test (CAT) was analysed in 1,817 patients from primary care in seven European countries. The CAT has a scoring range of 0-40 (high score representing poor health status). Mean CAT scores indicated significant health status impairment that was related to severity of airway obstruction, but within each Global Initiative for Obstructive Lung Disease stage (I to IV) there was a wide range of scores (I: 16.2 ± 8.8; II: 16.3 ± 7.9; III: 19.3 ± 8.2; and IV: 22.3 ± 8.7; I versus II, p = 0.88; II versus III, p<0.0001; III versus IV, p = 0.0001). CAT scores showed relatively little variability across countries (within ± 12% of the mean across all countries). Scores were significantly better in patients who were stable (17.2 ± 8.3) versus those suffering an exacerbation (21.3 ± 8.4) (p<0.0001); and in patients with no (17.3 ± 8.1) or one or two (16.6 ± 8.2) versus three or more (19.7 ± 8.5) comorbidities (p<0.0001 for both). The CAT distinguished between classes of other impairment measures and was strongly correlated with the St George's Respiratory Questionnaire (r = 0.8, p<0.0001). The CAT is a simple and easy-to-use questionnaire that distinguishes between patients of different degrees of COPD severity and appears to behave the same way across countries.

This review is the summary of a workshop on the role of distal airways in chronic obstructive pulmonary disease (COPD), which took place in 2009 in Vence, France. The evidence showing inflammation and remodelling in distal airways and the possible involvement of these in the pathobiology, physiology, clinical manifestations and natural history of COPD were examined. The usefulness and limitations of physiological tests and imaging techniques for assessing distal airways abnormalities were evaluated. Ex vivo studies in isolated lungs and invasive measurements of airway resistance in living individuals have revealed that distal airways represent the main site of airflow limitation in COPD. Structural changes in small conducting airways, including increased wall thickness and obstruction by muco-inflammatory exudates, and emphysema (resulting in premature airway closure), were important determinants of airflow limitation. Infiltration of small conducting airways by phagocytes (macrophages and neutrophils), dendritic cells and T and B lymphocytes increased with airflow limitation. Distal airways abnormalities were associated with patient-related outcomes (e.g. dyspnoea and reduced health-related quality of life) and with the natural history of the disease, as reflected by lung function decline and mortality. These data provide a clear rationale for targeting distal airways in COPD.

Classification of chronic obstructive pulmonary disease (COPD) is usually based on the severity of airflow limitation, which may not reflect phenotypic heterogeneity. Here, we sought to identify COPD phenotypes using multiple clinical variables. COPD subjects recruited in a French multicentre cohort were characterised using a standardised process. Principal component analysis (PCA) was performed using eight variables selected for their relevance to COPD: age, cumulative smoking, forced expiratory volume in 1 s (FEV(1)) (% predicted), body mass index, exacerbations, dyspnoea (modified Medical Research Council scale), health status (St George's Respiratory Questionnaire) and depressive symptoms (hospital anxiety and depression scale). Patient classification was performed using cluster analysis based on PCA-transformed data. 322 COPD subjects were analysed: 77% were male; median (interquartile range) age was 65.0 (58.0-73.0) yrs; FEV(1) was 48.9 (34.1-66.3)% pred; and 21, 135, 107 and 59 subjects were classified in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1, 2, 3 and 4, respectively. PCA showed that three independent components accounted for 61% of variance. PCA-based cluster analysis resulted in the classification of subjects into four clinical phenotypes that could not be identified using GOLD classification. Importantly, subjects with comparable airflow limitation (FEV(1)) belonged to different phenotypes and had marked differences in age, symptoms, comorbidities and predicted mortality. These analyses underscore the need for novel multidimensional COPD classification for improving patient care and quality of clinical trials.

The aim of the study was to determine whether the Borg dyspnoea scale could be a useful and simple marker to predict respiratory muscle weakness in amyotrophic lateral sclerosis (ALS). From April 1997 to 2001, respiratory function was perfomed in 72 patients together with the Borg score in both the upright (uBorg) and supine (sBorg) positions. Mean upright vital capacity (VC) was 81+/-24% predicted, sniff nasal inspiratory pressure (SNIP) was 55+/-26% pred, maximal inspiratory pressure (P(I,max)) was 57+/-26% pred and arterial carbon dioxide tension (P(a,CO(2))) was 41+/-6 mmHg. The mean Borg scores in the upright and supine positions were 1.7+/-1.5 and 2.2+/-2, respectively. A significant relationship between SNIP and uBorg (r = 0.4; p = 0.0007) and SNIP and sBorg (r = 0.58; p<0.0001) was observed. Upright VC, DeltaVC (measured as the supine fall in VC as a percentage of seated VC), P(I,max) and P(a,CO(2)) were significantly correlated with SNIP. A cut-off value of 3 on the sBorg scale provided the best sensitivity (80%) and specificity (78%) (area under the curve 0.8) to predict a SNIP < or =40 cmH(2)O, indicating severe inspiratory muscle weakness. Patients with a sBorg score > or =3 also exhibited significantly lower VC, P(I,max) and twitch mouth pressure during cervical magnetic stimulation, and slightly higher P(a,CO(2)) (43.7+/-7 versus 39.2+/-5 mmHg; p = 0.05). The Borg dyspnoea scale is a valuable noninvasive test for the prediction of inspiratory muscle weakness in ALS patients.

The present review is the summary of an expert workshop that took place in Vence (France) in 2007 on the role of distal airways in asthma. The evidence showing inflammation and remodelling in distal airways, and their possible involvement in asthma control and natural history, was reviewed. The usefulness and limitations of various techniques used for assessing distal airways were also evaluated, including pulmonary function tests and imaging. Finally, the available data studying the benefit of treatment better targeting distal airways in asthma was examined. It was concluded that both proximal and distal airways were involved in asthma and that distal airways were the major determinant of airflow obstruction. Inflammation in distal airways appeared more intense in severe and uncontrolled asthma. Distal airways were poorly attained by conventional aerosol of asthma medications owing to their granulometry, being composed of 3-5&emsp14;μm particles. Both proximal and distal airways might be targeted either by delivering medications systemically or by aerosol of extra-fine particles. Extra-fine aerosols of long-acting β-agonists, inhaled corticosteroids or inhaled corticosteroid/long-acting β-agonist combinations have been shown in short-term studies to be not inferior to non-extra-fine aerosols of comparators. However, available studies have not yet demonstrated that extra-fine inhaled medications offer increased benefit compared with usual aerosols in asthmatic patients.

Data on the individual and collective impact of chronic airflow obstruction at a population level are scarce. In a nationwide survey, dyspnoea, quality of life and missed working days were compared between subjects with and without spirometrically diagnosed chronic airflow obstruction. Subjects aged > or =45 yrs were recruited in French health prevention centres (n = 5,008). Results of pre-bronchodilator spirometry and questionnaires (European Community Respiratory Health Survey-derived questionnaire and European quality of life five-dimension questionnaire) were collected. Adequate datasets were available for 4,764 subjects aged 60+/-10 yrs (only 2% were aged > or =80 yrs). The prevalence of airflow obstruction (forced expiratory volume in one second/forced vital capacity of <0.70) was 7.5%. The vast majority (93.9%) of cases had not been diagnosed previously. Health status was significantly influenced by dyspnoea. Both were associated with the number of missed working days. Despite mild-to-moderate severity, subjects with chronic airflow obstruction exhibited more dyspnoea, poorer quality of life and higher numbers of missed working days (mean 6.71 versus 1.45 days.patient(-1).yr(-1) in patients without airflow obstruction, for the population with no known heart or lung disease). In conclusion, even mild-to-moderate airflow obstruction is associated with an impaired health status, which represents an additional argument in favour of early detection in chronic obstructive pulmonary disease.

Subclinical inflammation in gut mucosa has been demonstrated in bronchial asthma suggesting the whole mucosal system is involved in allergic diseases. The presence of subclinical bronchial involvement was assessed by nonspecific bronchial hyperresponsiveness (BHR) in nonasthmatic patients with food allergy (FA). BHR was studied in 35 patients with various manifestations of FA without food-induced asthma. Sixteen had a previous history of asthma and/or rhinitis to aeroallergens (group A), whereas 19 patients (group B) did not. BHR was defined by a provocative dose causing a 20% fall in forced expiratory volume in one second of (PC20) <8 mg.mL(-1) of methacholine. Asymptomatic BHR occurred frequently in nonasthmatic patients with FA (10 of 19, 53%); this did not significantly differ from patients with FA and a previous history of asthma and/or rhinitis to aeroallergens (13 of 16, 81%). PC20 was significantly lower in group A (1.84+/-0.53 mg.mL(-1)) than in group B (3.35+/-0.74 mg.mL(-1); p<0.05). The number of patients with positive skin tests to aeroallergens was similar between groups. Sequential evaluation, performed 1 year after initial evaluation, in 7 nonasthmatic patients (group B) demonstrated a similar level of BHR. The present study demonstrated that BHR is a frequent finding in nonasthmatic patients with food allergy which may be due, at least in part, to a subclinical inflammatory process in the bronchi.

Idiopathic pulmonary fibrosis (IPF) response to corticosteroids and cytotoxic medications appears to be the most important determinant of survival. The purpose of this retrospective study was to analyse the determinants of response to immunosuppressive therapy with prednisone alone, or prednisone and cyclophosphamide, in IPF. Twenty five consecutive patients were studied. Initial evaluation in untreated patients included clinical, biological and functional parameters. Sequential evaluation by pulmonary function tests (forced vital capacity (FVC) and transfer factor of the lungs for carbon monoxide (TLCO)) was performed at a 3 month interval. Response to therapy was defined as an improvement in FVC and/or TLCO of more than 10% after 12 months, with maintenance of this improvement for at least another 12 months. Twelve of the 25 patients were classified as responders. A symptomatic disease of less than 12 months duration before onset of therapy related to response. FVC was more impaired in the group of responders when the comparison was limited to patients with an FVC of less than 90%. Bronchoalveolar lavage cell counts were not significantly different between responders and non-responders. Assessment of pulmonary function after 3 months of treatment was predictive of maintenance of the response or of even further improvement. Patients with improved FVC after 3 months of therapy had a significantly shorter symptomatic disease before onset of treatment (7.6 +/- 7.1 vs 20.2 +/- 18.6 months). A beneficial effect of addition of cyclophosphamide was observed only in patients who demonstrated an early but short-lived improvement to steroids. Adverse reactions of immunosuppressive therapy were noticed in 10 patients, and required discontinuation of treatment in six of them.(ABSTRACT TRUNCATED AT 250 WORDS)

A subclinical inflammatory alveolitis as assessed by BAL cell analysis may be present in a high proportion of symptomless patients with immunological systemic disorders and with normal chest roentgenogram. Subclinical alveolitis can be characterized by the relative proportions of the different cell populations comprising the alveolitis and by the activated state of the cells. Thus, subclinical alveolitis can be classified into two major groups: lymphocyte and neutrophil alveolitis. Lymphocyte alveolitis is frequently found in patients with extrathoracic granulomatosis (Crohn's disease, primary biliary cirrhosis, extrathoracic sarcoidosis) or with some collagen vascular diseases (Sjögren's syndrome, rheumatoid arthritis, systemic lupus erythematosus). Neutrophil alveolitis is a main finding in collagen vascular diseases, especially progressive systemic sclerosis, dermatopolymyositis and mixed connective tissue disease. In addition, alveolar macrophages may be spontaneously activated and release various mediators that could be relevant to the pathogenesis of interstitial lung disease. On the other hand, some other alveolar macrophage functions (antibacterial activity may be severely impaired in some diseases, for example systemic lupus erythematosus). Alveolar inflammation is associated with an increase in the permeability of the alveolar membrane responsible for an increased influx of blood proteins in the alveolar spaces. Although subclinical inflammation may also be detected by high resolution computed tomography (HRCT) scan and/or lung permeability scintigraphic studies, the significance and prognostic value remains unclear and clearly differs according to both the disease and the pattern of alveolitis.

Interstitial lung disease (ILD) can be detected by pulmonary function testing (PFT) in 30-40% of rheumatoid arthritis (RA) patients. We assessed by bronchoalveolar lavage (BAL) the patterns of alveolitis in 21 RA patients: group 1 comprised 12 patients without evidence of ILD, and group 29 patients with clinical ILD defined by abnormal pulmonary function tests and/or chest X-ray. Cellular characteristics of BAL were studied in both groups. In addition, alveolar macrophages (AM) from patients in group 1 were isolated, and three parameters of cellular activation were studied: superoxide anion, fibronectin and neutrophil chemotactic activity generation. Total cell counts were not increased in group 1 but significantly increased in group 2 compared to controls. In group 1, 5/12 patients had elevated lymphocyte percentage (greater than 18%) suggesting subclinical lymphocyte alveolitis. In contrast, neutrophil alveolitis (greater than 4%) was found in 7/9 patients in group 2, mean percentage 12.9 +/- 4.2, compared with 1.2 +/- 6.4% in controls and 1.9 +/- 0.5% in group 1. These changes were not correlated with disease duration nor rheumatoid factor titres. Marked elevation of lymphocyte percentage was observed in patients with abnormal serum beta-2-microglobulin. Alveolar macrophages from group 1 patients released increased amounts of superoxide anion (7260 +/- 2700 vs controls 850 +/- 120 URL/5.10(5) cells), neutrophil chemotactic activity (21 +/- 4.8 vs controls 8.1 +/- 0.7 cells/HPF), and fibronectin (6.1 +/- 1.6 vs controls 1.3 +/- 0.2 ng.10(6) cells/hour). Whether or not lymphocyte alveolitis and/or AM dysfunction are pathogenic mechanisms of subsequent interstitial lung disease in patients who are still free of symptoms remains to be determined.