G. Garcia

Update on the roles of distal airways in asthma.

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.

Update on the roles of distal airways in COPD

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.

Recent advances in COPD: pathophysiology, respiratory physiology and clinical aspects, including comorbidities

Owing to its major and better recognised burden from both individual and societal perspectives, chronic obstructive pulmonary disease (COPD) is an area of intensive epidemiological, fundamental and clinical research, leading to the publication of more than 10,000 papers each year in the PubMed database. Among these, many report important advances in the understanding of and care for COPD. Epidemiological aspects are the topic of another manuscript in this issue of the European Respiratory Review [1], while the treatment of COPD and its exacerbations will be addressed in other reviews in upcoming issues. Thus, the present paper will focus on more fundamental aspects of pathophysiology, resting and exercise lung mechanics, respiratory muscles and gas exchange, together with more clinical topics, including respiratory symptoms and comorbidities. The purpose of the authors is clearly not to be exhaustive but to focus on points that are likely to have some impact on clinical practice in the relatively short term. Cigarette smoking is the leading cause of COPD in Western countries. Cigarette-associated noxious agents injure the airway epithelium and drive the key processes that lead to specific airway inflammation and structural changes [2]. Once these agents are removed, repair processes should, ideally, bring the airways back to their normal structure and function. In general, an inadequate repair process is thought to play a key role in the development of chronic airflow obstruction in some, but not all, smokers. Indeed, in many subjects most of the inflammatory changes continue despite smoking cessation [3]. This failure of bronchial inflammation to resolve might contribute to systemic changes and ongoing bronchial and lung matrix degradation. In addition to persistent airway inflammation, other major phenomena involved in the disease initiation and progression include increased oxidative stress and protease–antiprotease imbalance. Several studies have established that …

The association between resting and mild-to-moderate exercise pulmonary artery pressure

The mean pulmonary artery pressure (P̄pa) achieved on mild-to-moderate exercise is age related and its haemodynamic correlates remain to be documented in patients free of pulmonary hypertension (PH). Our retrospective study involved patients free of PH investigated in our centre for possible pulmonary vascular disease between January 1, 2007 and October 31, 2009 who underwent right heart catheterisation at rest and during supine exercise up to 60 W. The 38 out of 99 patients aged <50 yrs were included and a P̄pa of 30 mmHg was considered the upper limit of normal on exercise. The 24 subjects who developed P̄pa>30 mmHg on exercise had higher resting P̄pa (19±3 versus 15±4 mmHg) and indexed pulmonary vascular resistance (PVRi; 3.4±1.5 versus 2.2±1.1 WU·m2; p<0.05) than the remaining 14 subjects. Resting P̄pa >15 mmHg predicted exercise P̄pa >30 mmHg with 88% sensitivity and 57% specificity. The eight patients with resting P̄pa 22–24 mmHg all had exercise P̄pa >30 mmHg. In subjects aged <50 yrs investigated for possible pulmonary vascular disease and free of PH, patients with mild-to-moderate exercise P̄pa >30 mmHg had higher resting PVRi and higher resting P̄pa, although there was no resting P̄pa threshold value that could predict normal response on mild-to-moderate exercise. The clinical relevance of such findings deserves further long-term follow-up studies.

Association of pulmonary aspergilloma and allergic bronchopulmonary aspergillosis.

To the Editors: We have read with interest recent reports on the complex interactions between Aspergillus fumigatus and the lungs [1–3]. A. fumigatus may be involved in different respiratory diseases including aspergilloma, allergic bronchopulmonary aspergillosis (ABPA) or invasive infectious manifestations. However, these different manifestations are usually not concomitantly present and there are only a few studies that report the association between these complications [4–14]. We wish to present a case of fully documented aspergilloma and ABPA in a patient with difficult asthma, which represented a difficult therapeutic challenge. A 50-yr-old female, nonsmoker was followed up since 2000 for difficult to control non-atopic asthma associated with severe rhinosinusitis. In March 2008, the patient presented to the respiratory department (Hopital Antonie Beclere, Clamart, France) with a 1-month history of mild recurrent haemoptysis. Physical examination was normal. Chest radiography showed excavated lung opacity in the superior left field. A thoracic computed tomography (CT) scan revealed a cavity with a fungus ball in the left upper lobe and two other opacities in the left lower lobe (fig. 1). There was no fungus ball in the sinuses. …

Mise à jour des recommandations (2015) pour la prise en charge et le suivi des patients asthmatiques adultes et adolescents (de 12 ans et plus) sous l’égide de la Société de pneumologie de langue française (SPLF) (texte court)

a Université de Bordeaux, Inserm U1219, ISPED, CHU de Bordeaux, service des maladies respiratoires, pôle cardio-thoracique, 33000 Bordeaux, France b Université Montpellier 1, Inserm U1046, CHU de Montpellier, département de pneumologie et addictologie, hôpital Arnaud-de-Villeneuve, 34000 Montpellier, France c Université de Bourgogne, Inserm U866, CHU de Bourgogne, service de pneumologie et soins intensifs respiratoires, 21079 Dijon, France d Université de Reims—Champagne-Ardennes, CHU Maison-Blanche, service de pneumologie, 51000 Reims, France e Université Paris—Sud, Faculté de Médecine, AP—HP, Centre National de Référence de l’Hypertension Pulmonaire Sévère, Département Hospitalo-Universitaire (DHU) Thorax Innovation, UMRS 999, Inserm, Hôpital de Bicêtre, service de pneumologie, 94270 Le Kremlin-Bicêtre, France f Université de Bretagne Occidentale, CHU de la Cavale-Blanche, département de médecine interne et de pneumologie, 29000 Brest, France g Université Paris-Diderot, AP—HP, hôpital Bichat, service de pneumologie, Centre de compétence des maladies pulmonaires rares, département hospitalo-universitaire FIRE, 75018 Paris, France