Background: Despite improvement in lung function, most lung transplant (LTx) recipients show an unexpectedly reduced exercise capacity that could be explained by persisting peripheral muscle dysfunction of multifactorial origin. We analyzed the course of symptoms, including dyspnea, muscle effort and muscle pain and its relation with cardiac and pulmonary function parameters during an incremental exercise testing.Methods: Twenty-four bilateral LTx recipients were evaluated in an observational cross-sectional study. Recruited patients underwent incremental cardio-pulmonary exercise testing (CPET). Arterial blood gases at rest and peak exercise were measured. Dyspnea, muscle effort and muscle pain were scored according to the Borg modified scale. Potential associations between the severity of symptoms and exercise testing parameters were analyzed using a Forest-Tree Machine Learning approach, which accomplishes for a ratio between number of observations and number of screened variables less than unit.Results: Dyspnea score was significantly associated with maximum power output (WR, watts), and minute ventilation (VE, L/min) at peak exercise. In a controlled subgroup analysis, dyspnea score was a limiting symptom only in LTx recipients who reached the higher levels of WR (≥ 101 watts) and V_E(≥ 53 L/min). Muscle effort score was significantly associated with breathing reserve as percent of maximal voluntary ventilation (BR%MVV). The lower the BR%MVV at peak exercise (< 32) the higher the muscle effort perception. Muscle pain score was significantly associated with VO₂peak, arterial [HCO₃⁻] at rest, and V_E/VCO₂slope. In a subgroup analysis, muscle pain was the limiting symptom in LTx recipients with a lower VO₂peak (< 15 mL/Kg/min) and a higher V_E/VCO₂slope (≥ 32).Conclusions: The majority of our LTx recipients reported peripheral limitation as the prevalent reason for exercise termination. Muscle pain at peak exercise was strictly associated with basal and exercise-induced metabolic altered pathways. The onset of dyspnea (breathing effort) was associated with the intensity of ventilatory response to meet metabolic demands for increasing WR. Our study suggests that only an accurate assessment of symptoms combined with cardio-pulmonary parameters allows a correct interpretation of exercise limitation and a tailored exercise prescription. The role and mechanisms of muscle pain during exercise in LTx recipients requires further investigations.

Objectives: The effect of induction chemotherapy (IC) on lung function and exercise capacity in patients with malignant pleural mesothelioma (MPM) has not been largely examined. The aim of this study was to evaluate the changes in pulmonary function and oxygen consumption following IC in patients with MPM. Methods: Between 2004 and 2009, 36 consecutive patients (mean age 62.1 ± 1.5 years, M/F = 25/11) were prospectively investigated. Data concerning medical history, histology, staging and response to chemotherapy were collected. All patients underwent pulmonary function test before (in the absence of pleural effusion) and after chemotherapy (platinum-based agent plus pemetrexed); 23 out of 36 patients also performed a cardiopulmonary incremental exercise test. Results: An epithelioid histotype was documented in 88.8% of patients. A partial response to chemotherapy was observed in 44.5% of cases and 36.1% of patients experienced grade 2–3 toxicity. A significant improvement in forced expiratory volume in 1 s (FEV₁) (0.13 ± 0.30 l; P = 0.01), in VO₂ peak (1.76 ± 2.91 ml kg⁻¹ min⁻¹; P = 0.005), in PaO₂ at rest (4.76 ± 9.84 mmHg; P = 0.03) and in PaO₂ at peak exercise (6.26 ± 12.72 mmHg; P = 0.04) was detected. The diffusion capacity of the lung for carbon monoxide (DLCO) also increased (1.25 ± 4.68 ml min⁻¹ mmHg⁻¹), although not significantly (P = 0.20). The stratified analysis based on the response to IC showed a significant improvement in FEV₁, forced vital capacity (FVC) and vital capacity (VC) (both absolute and percentage of predicted values) only in patients with a partial response. Conclusions: An improvement in lung function and exercise capacity was seen after IC in patients with MPM. These data suggest that IC does not compromise cardiopulmonary performance in this subset of patients.

Background: Patients with COVID-19 may experience hypoxemic Acute Respiratory Failure (hARF) requiring O₂-therapy by High-Flow Nasal Cannula (HFNO). Although Prone Positioning (PP) may improve oxygenation in COVID-19 non-intubated patients, the results on its clinical efficacy are controversial. The present study aims to prospectively investigate whether PP may reduce the need for endotracheal intubation (ETI) in patients with COVID-19 receiving HFNO. Methods: All consecutive unselected adult patients with bilateral lung opacities on chest X-ray receiving HFNO after admission to a SARS-CoV-2 Respiratory Intermediate Care Unit (RICU) were considered eligible. Patients who successfully passed an initial PP trial (success group) underwent PP for periods ≥ 2 h twice a day, while receiving HFNO. The study’s primary endpoint was the intubation rate during the stay in the RICU. Results: Ninety-three patients were included in the study. PP was feasible and safe in 50 (54%) patients. Sixteen (17.2%) patients received ETI and 27 (29%) escalated respiratory support, resulting in a mortality rate of 9/93 (9.7%). The length of hospital stay was 18 (6–75) days. In 41/50 (80%) of subjects who passed the trial and underwent PP, its use was associated with clinical benefit and survival without escalation of therapy. Conclusions: PP is feasible and safe in over 50% of COVID-19 patients receiving HFNO for hARF. Randomized trials are required to confirm that PP has the potential to reduce intubation rate.

Background: The efficacy and effectiveness of nintedanib as a first-line therapy in idiopathic pulmonary fibrosis (IPF) patients have been demonstrated by clinical trials and real-life studies. Our aim was to examine the safety profile and effectiveness of nintedanib when it is utilized as a second-line treatment in subjects who have discontinued pirfenidone. Methods: The medical charts of 12 patients who were switched from pirfenidone to nintedanib were examined retrospectively. The drug’s safety was defined by the number of adverse events (AEs) that were reported; disease progression was evaluated based on the patient’s vital status and changes in forced vital capacity (FVC) at 12-month follow-up. Results: The numbers of patients experiencing AEs and of the AEs per patient in our study group didn’t significantly differ with respect to a group of 56 individuals who were taking nintedanib as a first-line therapy during the study period (5/12 vs. 22/56; p = 0.9999, and 0.00 (0.00–1.00) vs. 0.00 (0.00–3.00); p = 0.517, respectively). Two out of the 3 patients who had been switched to nintedanib due to a rapid disease progression showed stabilized FVC values. Conclusions: Nintedanib was found to have an acceptable safety profile in the majority of the IPF patients switched from pirfenidone. Prospective studies are warranted to determine if the drug can effectively delay disease progression in these patients.