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Background: The natural history of asthma severity is poorly known. Objective: To investigate prognostic factors of asthma severity. Methods: All current patients with asthma identified in 1991 to 1993 in the European Community Respiratory Health Survey were followed up, and their severity was assessed in 2002 by using the Global Initiative for Asthma categorization (n = 856). Asthma severity (remittent, intermittent, mild, moderate, severe) was related to potential determinants evaluated at baseline and during the follow-up by a multinomial logistic model, using the intermittent group as the reference category for relative risk ratios (RRRs). Results: Asthma severity measured at baseline was a determinant of a patient''s severity at the end of the follow-up. At baseline, severe persistent had a poorer FEV1% predicted, a poorer symptom control, higher IgE levels (RRR, 2.06; 95% CI, 1.38-3.06), and a higher prevalence of chronic cough/mucus hypersecretion (RRR, 4.90; 95% CI, 2.18-11.02) than patients with intermittent asthma. Moderate persistent showed the same prognostic factors as severe persistent, even if the associations were weaker. Mild persistent had a distribution of prognostic factors that was similar to patients with intermittent asthma, although the former showed a poorer symptom control than the latter. Remission mainly occurred in patients with less severe asthma and was negatively associated with a change in body mass index (RRR, 0.86; 95% CI, 0.75-0.97). Allergic rhinitis, smoking, and respiratory infections in childhood were not associated with asthma severity. Conclusion: Patients with moderate and severe persistent asthma are characterized by early deterioration of lung function. High IgE levels and persistent cough/mucus hypersecretion are strong markers of moderate/severe asthma, which seems to be a different phenotype from mild persistent or intermittent asthma. Clinical implications: Our results suggest that the evolution of asthma severity is to a large extent predictable. [Copyright &y& Elsevier]

Summary: An unusual case of smoking-related centrilobular emphysema with normal spirometry. A 64-year-old man presented with severe dyspnoea and respiratory failure. Pulmonary function and mechanics were normal except for a marked reduction in diffusing capacity of the lung. High-resolution CT scan showed diffuse centrilobular emphysema also involving lower lobes. Pulmonary embolism, cardiac or pulmonary shunt and immunopathologically based vasculitis were excluded. Pulmonary pressure was at the upper limit of normality but within few months he developed a severe pulmonary hypertension. Although spirometry is the only physiologic measure recommended by the updated Global Initiative for Chronic Obstructive Lung Disease guidelines for confirming the diagnosis it should be recognized that diffuse emphysema may occur with only abnormalities in gas exchange without airflow obstruction. The identification of different phenotypes within COPD is important for understanding disease heterogeneity and progression. [Copyright &y& Elsevier]

Pulmonary acute and chronic diseases, such as chronic obstructive pulmonary disease, pulmonary fibrosis and pulmonary hypertension, are considered to be major health issues worldwide. Cellular therapies with Mesenchymal Stem Cells (MSCs) offer a new therapeutic approach for chronic and acute lung diseases related to their anti-inflammatory, immunomodulatory, regenerative, pro-angiogenic and anti-fibrotic properties. Such therapeutic effects can be attributed to MSC-secretome, made of free soluble proteins and extracellular vesicles (EVs). This review summarizes the recent findings related to the efficacy and safety of MSC-derived products in pre-clinical models of lung diseases, pointing out the biologically active substances contained into MSC-secretome and their mechanisms involved in tissue regeneration. A perspective view is then provided about the missing steps required for the secretome "pharmaceuticalization" into a high quality, safe and effective medicinal product, as well as the formulation strategies required for EV non-invasive route of administration, such as inhalation. Unlabelled Image • MSC-secretome is proposed as cell substitute in acute and chronic lung diseases. • MSC-secretome has immunomodulatory, pro-angiogenetic and anti-protease properties. • MSC-secretome is safe and effective in pre-clinical models of lung diseases. • MSC-secretome must be formulated into quality, safe and effective medicinal product. • MSC-secretome intravenous and/or inhalation pharmaceutical dosage forms are needed. [ABSTRACT FROM AUTHOR]