Patients with idiopathic pulmonary fibrosis (IPF) frequently have a substantial burden of comorbidities [1]. Antifibrotic therapy is recommended to slow the progression of IPF [2]. Patients receiving antifibrotic therapy frequently receive concomitant medications for the management of comorbidities [1, 3–9]. Previous post hoc analyses of antacids, statins, metformin, anticoagulants and angiotensin modulators in patients with IPF enrolled in phase III randomised controlled trials (RCTs) have generated hypotheses on the impact of these treatments on IPF outcomes [3–9]. The effects of multiple concomitant medications in patients with IPF have been largely unexplored. The objective of the present analyses was to explore the association between use of combinations of frequently prescribed concomitant medications and disease outcomes in patients with IPF.

Rationale Precapillary pulmonary hypertension (PH) is a devastating complication of sickle cell disease (SCD). Little is known about the influence of the SCD genotype on PH characteristics. Objectives To describe clinical phenotypes and outcomes of precapillary PH due to SCD according to disease genotype. Methods A nationwide multicentre retrospective study including all patients with SCD-related precapillary PH from the French PH Registry was conducted. Clinical characteristics and outcomes according to SCD genotype were analysed. Results 58 consecutive SCD patients with precapillary PH were identified, of whom 41 had homozygous for haemoglobin S (SS) SCD, three had S-β 0 thalassaemia (S-β 0 thal) and 14 had haemoglobin SC disease (SC). Compared to SC patients, SS/S-β 0 thal patients were characterised by lower 6-min walk distance (p=0.01) and lower pulmonary vascular resistance (p=0.04). Mismatched segmental perfusion defects on lung scintigraphy were detected in 85% of SC patients and 9% of SS/S-β 0 thal patients, respectively, and 50% of SS/S-β 0 thal patients had heterogeneous lung perfusion without segmental defects. After PH diagnosis, 31 patients (53%) received medical therapies approved for pulmonary arterial hypertension, and chronic red blood cell exchange was initiated in 23 patients (40%). Four patients were managed for chronic thromboembolic PH by pulmonary endarterectomy (n=1) or balloon pulmonary angioplasty (n=3). Overall survival was 91%, 80% and 60% at 1, 3 and 5 years, respectively, without influence of genotype on prognosis. Conclusions Patients with precapillary PH related to SCD have a poor prognosis. Thrombotic lesions appear as a major component of PH related to SCD, more frequently in SC patients.

Sarcoidosis is a complex disease characterised by the presence of epithelioid non-caseating granulomatous inflammation affecting multiple organs and whose aetiology has been related to microbial, environmental and genetic factors [1, 2]. However, no single antigenic trigger has been identified, although associations with Propionibacterium acnes and mycobacteria pathogen-associated molecular pattern, deposition of serum amyloid A, and exposure to inorganic particles and insecticides have been suggested [3–5]. Occurrence of familial cases suggests that genetic variation contributes to disease pathogenesis with a heritability of about 39% [6]. Despite intensive genome-wide association studies, no single nucleotide polymorphism is, as yet, able to explain the “missing heritability” in the disease, especially for non-resolving, non-Löfgren syndrome sarcoidosis .We read with interest the research letter by REINIKOVAITE et al. [1], in which the authors reported same level of damage in the lungs of Sprague Dawley rats subjected to whole body chronic exposure of e-cigarette vapour emissions and cigarette smoke, as well as to subcutaneous injection of nicotine. Their conclusion is that e-cigarette use and long-time consumption of nicotine are just as toxic as tobacco cigarettes. We appreciate the authors’ intention to address concerns related to the potential long-term health effects of e-cigarette use and nicotine exposure, but there are a number of methodological considerations that lessen the impact of their findings.