BackgroundThe coronavirus infectious disease (COVID-19) pandemic is an ongoing global health care challenge. Up to one third of hospitalised patients develop severe pulmonary complications and ARDS. Pulmonary outcomes following COVID-19 are unknown.MethodsThe Swiss COVID-19 lung study is a multicentre prospective cohort investigating pulmonary sequela of COVID-19. We report on initial follow-up 4 months after mild/moderate or severe/critical COVID-19 according to the WHO severity classification.Results113 COVID-19 survivors were included (mild/moderate 47, severe/critical 66). We confirmed several comorbidities as risk factors for severe/critical disease. Severe/critical disease was associated with impaired pulmonary function, i.e. diffusing capacity (DLCO) %-predicted, reduced 6-MWD, and exercise-induced oxygen desaturation. After adjustment for potential confounding by age, sex, and BMI, patients after severe/critical COVID-19 had a 20.9 (95% CI 12.4–29.4, p=0.01) lower DLCO %-predicted at follow up. DLCO %-predicted was the strongest independent factor associated with previous severe/critical disease when age, sex, BMI, 6MWD, and minimal SpO2 at exercise, were included in the multivariable model (adjusted odds ratio [OR] per 10%-predicted 0.59 [95% CI 0. 37–0.87], p=0.01). Mosaic hypoattenuation on chest computed tomography at follow-up was significantly associated with previous severe/critical COVID-19 including adjustment for age and sex (adjusted OR 11.7 [95%CI 1.7–239), p=0.03).ConclusionsFour months after SARS CoV-2 infection, severe/critical COVID-19 was associated with significant functional and radiological abnormalities, potentially due to small airway and lung parenchymal disease. A systematic follow-up for survivors needs to be evaluated to optimise care for patients recovering from COVID-19.

Infliximab therapy resulted in a statistically significant improvement in % predicted FVC at Week 24. The clinical importance of this finding is not clear. The results of this Phase 2 clinical study support further evaluation of anti-TNF-alpha therapy in severe, chronic, symptomatic sarcoidosis.

Nonlinear regression models are applied in a broad variety of scientific fields. Various R functions are already dedicated to fitting such models, among which the function nls() has a prominent position. Unlike linear regression fitting of nonlinear models relies on non-trivial assumptions and therefore users are required to carefully ensure and validate the entire modeling. Parameter estimation is carried out using some variant of the leastsquares criterion involving an iterative process that ideally leads to the determination of the optimal parameter estimates. Therefore, users need to have a clear understanding of the model and its parameterization in the context of the application and data considered, an a priori idea about plausible values for parameter estimates, knowledge of model diagnostics procedures available for checking crucial assumptions, and, finally, an understanding of the limitations in the validity of the underlying hypotheses of the fitted model and its implication for the precision of parameter estimates. Current nonlinear regression modules lack dedicated diagnostic functionality. So there is a need to provide users with an extended toolbox of functions enabling a careful evaluation of nonlinear regression fits. To this end, we introduce a unified diagnostic framework with the R package nlstools. In this paper, the various features of the package are presented and exemplified using a worked example from pulmonary medicine.

Decreasing exposure to airborne particulates appears to attenuate the decline in lung function related to exposure to PM10. The effects are greater in tests reflecting small-airway function.

Pulmonary hypertension during exercise is common in severe chronic obstructive pulmonary disease (COPD). It was hypothesised that the use of the endothelin-receptor antagonist bosentan can improve cardiopulmonary haemodynamics during exercise, thus increasing exercise tolerance in patients with severe COPD.In the present double-blind, placebo-controlled study, 30 patients with severe or very severe COPD were randomly assigned in a 2:1 ratio to receive either bosentan or placebo for 12 weeks. The primary end-point was change in the 6-min walking distance. Secondary end-points included changes in health-related quality of life, lung function, cardiac haemodynamics, maximal oxygen uptake and pulmonary perfusion patterns.Compared with placebo, patients treated with bosentan during 12 weeks showed no significant improvement in exercise capacity as measured by the 6-min walking distance (mean¡SD 331¡123 versus 329¡94 m). There was no change in lung function, pulmonary arterial pressure, maximal oxygen uptake or regional pulmonary perfusion pattern. In contrast, arterial oxygen pressure dropped, the alveolar-arterial gradient increased and quality of life deteriorated significantly in patients assigned bosentan.The oral administration of the endothelin receptor antagonist bosentan not only failed to improve exercise capacity but also deteriorated hypoxaemia and functional status in severe chronic obstructive pulmonary disease patients without severe pulmonary hypertension at rest. KEYWORDS: Endothelin-receptor antagonist, exercise capacity, pulmonary hypertension, treatment P ulmonary hypertension (PH) at rest and during exercise is a very frequent complication in the natural history of chronic obstructive pulmonary disease (COPD) [1,2]. Correspondingly, this condition has been reported in 20-91% of patients with severe COPD and/or emphysema [3,4]. The presence of PH is commonly associated with more frequent use of healthcare resources and worse clinical outcome [5]. Remarkably, pulmonary artery pressure has been suggested to be the single best predictor of mortality in COPD [6].In COPD, PH is generally of moderate severity, but the range of mean pulmonary artery pressures varies substantially [7]. Moderate and severe PH are present in 9.8 and 3.7%, respectively, of the patients undergoing right heart catheterisation before lung volume reduction surgery [7]. Despite many uncertainties, studies indicate that 35% of all patients with severe COPD have pulmonary artery pressures of .20 mmHg at rest [8]. In addition, pulmonary pressures during exercise are greater than predicted by the pulmonary vascular resistance (PVR) equation in COPD, suggesting active pulmonary vasoconstriction on exertion [9]. Hence, of those patients without PH at rest, a further 52% are estimated to develop PH during exercise [5].There are many pathological similarities between idiopathic pulmonary arterial hypertension (PAH) and PH related to COPD. Like idiopathic PAH, pulmonary arteries in patients with COPD show evidence of fibromuscula...

OBJECTIVES: The Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA) was designed to investigate the health effects from long-term exposure to air pollution. METHODS: The health assessment at recruitment (1991) and at the first reassessment (2001-3) consisted of an interview about respiratory health, occupational and other exposures, spirometry, a methacholine bronchial challenge test, end-expiratory carbon monoxide (CO) measurement and measurement for atopy. A bio bank for DNA and blood markers was established. Heart rate variability was measured using a 24-hour ECG (Holter) in a random sample of participants aged 50 years and older. Concentrations of nitrogen dioxide (NO2), sulphur dioxide (SO2), ozone (O3) and particulates in ambient air have been monitored in all study areas since 1991. Residential histories collected over the 11 year follow-up period coupled with GIS modelling will provide individual long-term air pollutant exposure estimates. RESULTS: Of 9651 participants examined in 1991, 8715 could be traced for the cohort study and 283 died. Basic information about health status was obtained for 8047 individuals (86% of alive persons), 6 528 individuals (70%) agreed to the health examination and 5 973 subjects (62%) completed the entire protocol. Non-participants in the reassessment were on average younger than participants and more likely to have been smokers and to have reported respiratory symptoms in the first assessment. Average weight had increased by 5.5 kg in 11 years and 28% of smokers in 1991 had quit by the time of the reassessment. The most powerful approach for studying long-term effects from ambient air pollution on health is the long-term prospective follow-up of well-defined population-based cohorts with well-characterized air pollution exposure information (European Science Foundation 1998). There are currently only five cohort studies in adults, with published results, that address the long-term impact of air pollution (Abbey et al. 1999;Dockery et al. 1993;Finkelstein et al. 2004;Hoek et al. 2002; Pope et al. 2002;. All studies but one are based in the US and three of them (Dockery et al. 1993;Hoek et al. 2002; Pope et al. 2002), have only published findings related to mortality. The relation of longterm exposure to air pollution with respiratory and cardiovascular health and morbidity has yet to be measured in a large prospective cohort study in Europe. The large European Community Respiratory Health Survey (ECRHS) de- Probst-Hensch NM, et al. Follow-up of SAPALDIA 2, 1991-2003 signed to measure natural history and risk factors for respiratory diseases (particularly asthma and allergy) across Europe has recently included air pollution exposure assessment in its protocol (Burney et al. 1994;Hazenkamp-von Arx et al. 2004). However, the Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA) is the only prospective cohort study of respiratory and cardiovascular health in adults in Europe with detailed individual residential exposure hi...

The aim of the present study was to investigate the efficacy of infliximab for the treatment of extrapulmonary sarcoidosis.A prospective, randomised, double-blind, placebo-controlled trial was conducted, with infliximab at 3 and 5 mg?kg -1 body weight administered over 24 weeks. Extrapulmonary organ severity was determined by a novel severity tool (extrapulmonary physician organ severity tool; ePOST) with an adjustment for the number of organs involved (ePOSTadj). In total, 138 patients enrolled in the trial of infliximab versus placebo for the treatment of chronic corticosteroiddependent pulmonary sarcoidosis. The baseline severity of extrapulmonary organ involvement, as measured by ePOST, was similar across treatment groups. After 24 weeks of drug-therapy study, the change from baseline to week 24 in ePOST was greater for the combined infliximab group compared with the placebo group. After adjustment for the number of extrapulmonary organs involved, the improvement in ePOSTadj observed in the combined infliximab group was also greater than that observed in placebo-treated patients, after 24 weeks of therapy. The improvements in ePOST and ePOSTadj were not maintained during a subsequent 24-week washout period.Infliximab may be beneficial compared with placebo in the treatment of extrapulmonary sarcoidosis in patients already receiving corticosteroids, as assessed by the severity tool described in the present study.

Of patients awaiting lung transplantation, the death rates are highest in those with idiopathic pulmonary fibrosis (IPF), suggesting that many IPF patients are referred late for transplantation. Therefore this study was undertaken to evaluate baseline pulmonary function test (PFT) and high-resolution computed tomography (HRCT) fibrosis scores, and the relationship to survival in IPF patients younger than 65 yr of age. A total of 115 patients with usual interstitial pneumonia (UIP) were studied. At presentation to a tertiary referral center, PFT and HRCT data were collected and analyzed for prognostic significance: the primary outcome measure was patient death. Based on the length of the waiting list for transplantation, prediction of 2-yr survival was examined. DL(CO) percent predicted and HRCT-fibrosis score were found to be independent predictors of survival and in combination gave the best prognostic prediction. The optimal points on the receiver operating characteristic (ROC) curves for discriminating between survivors and nonsurvivors corresponded to 39% DL(CO) percent predicted, and to a HRCT-fibrosis score of 2.25. The combination of these parameters yielded an optimal point with a specificity and a sensitivity of 84% and 82%, respectively. A model based on a combination of DL(CO) percent predicted and HRCT-fibrosis score may optimize the timing of referral for transplantation.