Assessing quality of life of idiopathic pulmonary fibrosis patients: the INSTAGE study

Kolb M, et al. Nintedanib plus sildenafil in patients with idiopathic pulmonary fibrosis. N Engl J Med 2018; 379: 1722–1731

Salivary immunity and lower respiratory tract infections in non-elite marathon runners

Peer ReviewedPostprint (published version

Bronchiectasis-COPD Overlap Syndrome: Role of Peripheral Eosinophil Count and Inhaled Corticosteroid Treatment

Both chronic obstructive pulmonary disease and bronchiectasis are highly prevalent diseases. In both cases, inhaled corticosteroids (ICs) are associated with a decrease in exacerbations in patients with a high peripheral blood eosinophil count (BEC), but it is still not known what occurs in bronchiectasis-COPD overlap syndrome (BCOS). The present study aimed to assess the effect of ICs on various outcomes in patients with BCOS, according to BEC values. We undertook a post-hoc analysis of a cohort of 201 GOLD II-IV COPD patients with a long-term follow-up (median 74 [IQR: 40-106] months). All participants underwent computerized tomography and 115 (57.2%) had confirmed BCOS. A standardized clinical protocol was followed and two sputum samples were collected at each medical visit (every 3-6 months), whenever possible. During follow-up, there were 68 deaths (59.1%), and the mean rate of exacerbations and hospitalizations per year was 1.42 (1.2) and 0.57 (0.83), respectively. A total of 44.3% of the patients presented at least one pneumonic episode per year. The mean value of eosinophils was 402 (112) eosinophils/mu L, with 27 (23.5%), 63 (54.8%), and 25 patients (21.7%) presenting, respectively, less than 100, 101-300, and more than 300 eosinophils/mu L. A total of 84 patients (73.1%) took ICs. The higher the BEC, the higher the annual rate of exacerbations and hospitalizations. Patients with less than 100 eosinophils/mu L presented more infectious events (incident exacerbations, pneumonic episodes, and chronic bronchial infection via pathogenic bacteria). Only those patients with eosinophilia (>300 eosinophils/mu L) treated with ICs decreased the number (1.77 (1.2) vs. 1.08 (0.6), p < 0.001) and the severity (0.67 (0.8) vs. 0.35 (0.5), p = 0.011) of exacerbations, without any changes in the other infectious outcomes or mortality. In conclusion, ICs treatment in patients with BCOS with increased BEC decreased the number and severity of incident exacerbations without any negative influence on other infectious outcomes (incidence of pneumonia or chronic bronchial infection)

Antimicrobial peptides, disease severity and exacerbations in bronchiectasis

Rationale: Recently a frequent exacerbator phenotype has been described in bronchiectasis, but the underlying biological mechanisms are unknown. Antimicrobial peptides (AMPs) are important in host defence against microbes but can be proinflammatory in chronic lung disease. Objectives: To determine pulmonary and systemic levels of AMP and their relationship with disease severity and future risk of exacerbations in bronchiectasis. Methods: A total of 135 adults with bronchiectasis were prospectively enrolled at three European centres. Levels of cathelicidin LL-37, lactoferrin, lysozyme and secretory leucocyte protease inhibitor (SLPI) in serum and sputum were determined at baseline by ELISA. Patients were followed up for 12 months. We examined the ability of sputum AMP to predict future exacerbation risk. Measurements and main results: AMP levels were higher in sputum than in serum, suggesting local AMP release. Patients with more severe disease at baseline had dysregulation of airway AMP. Higher LL-37 and lower SLPI levels were associated with Bronchiectasis Severity Index, lower FEV1 (forced expiratory volume in 1 s) and Pseudomonas aeruginosa infection. Low SLPI levels were also associated with the exacerbation frequency at baseline. During follow-up, higher LL-37 and lower SLPI levels were associated with a shorter time to the next exacerbation, whereas LL-37 alone predicted exacerbation frequency over the next 12 months. Conclusions: Patients with bronchiectasis showed dysregulated sputum AMP levels, characterised by elevated LL-37 and reduced SLPI levels in the frequent exacerbator phenotype. Elevated LL-37 and reduced SLPI levels are associated with Pseudomonas aeruginosa infection and can predict future risk of exacerbations in bronchiectasis

Clinical Outcomes of Severe COVID-19 Patients Admitted to an Intermediate Respiratory Care Unit

Introduction: Many severe COVID-19 patients require respiratory support and monitoring. An intermediate respiratory care unit (IMCU) may be a valuable element for optimizing patient care and limited health-care resources management. We aim to assess the clinical outcomes of severe COVID-19 patients admitted to an IMCU. Methods: Observational, retrospective study including patients admitted to the IMCU due to COVID-19 pneumonia during the months of March and April 2020. Patients were stratified based on their requirement of transfer to the intensive care unit (ICU) and on survival status at the end of follow-up. A multivariable Cox proportional hazards method was used to assess risk factors associated with mortality. Results: A total of 253 patients were included. Of them, 68% were male and median age was 65 years (IQR 18 years). Ninety-two patients (36.4%) required ICU transfer. Patients transferred to the ICU had a higher mortality rate (44.6 vs. 24.2%; p < 0.001). Multivariable proportional hazards model showed that age ≥65 years (HR 4.14; 95%CI 2.31-7.42; p < 0.001); chronic respiratory conditions (HR 2.34; 95%CI 1.38-3.99; p = 0.002) and chronic kidney disease (HR 2.96; 95%CI 1.61-5.43; p < 0.001) were independently associated with mortality. High-dose systemic corticosteroids followed by progressive dose tapering showed a lower risk of death (HR 0.15; 95%CI 0.06-0.40; p < 0.001). Conclusions: IMCU may be a useful tool for the multidisciplinary management of severe COVID-19 patients requiring respiratory support and non-invasive monitoring, therefore reducing ICU burden. Older age and chronic respiratory or renal conditions are associated with worse clinical outcomes, while treatment with systemic corticosteroids may have a protective effect on mortality