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Patients with autoimmune pulmonary alveolar proteinosis received inhaled molgramostim or matching placebo for 24 weeks. Patients receiving molgramostim had greater improvement in pulmonary gas transfer and alleviation of symptoms than those receiving placebo.

Background: A diagnostic lung biopsy may be required in some cases of fibrotic interstitial lung diseases (ILD). Transbronchial cryobiopsy has been suggested as a possible alternative to surgical lung biopsy. However, previous estimates of its diagnostic yield were not validated compared to the definitive diagnosis in explanted lungs. Objectives: We aimed to assess the diagnostic accuracy of cryobiopsy in fibrotic ILD patients who subsequently had lung transplantation. Methods: All 197 patients who underwent lung transplantation at our Center due to fibrotic ILD from January 2010 to May 2018, were screened for the presence of a pre-transplant cryobiopsy. Fourteen patients who underwent cryobiopsy before transplantation were identified. Two expert lung pathologists blindedto the explant diagnoses, independently examined these cryobiopsy specimens to decide if they match guideline criteria for usual interstitial pneumonia (UIP) pattern or an alternative diagnosis. The primary measure was the diagnostic accuracy of cryobiopsy to detect or refute a UIP pattern, as compared to the final explant diagnosis. Results: Median time between cryobiopsy and transplantation was 1.4 years. All 14 cryobiopsy samples contained adequate alveolar tissue. The explant diagnosis of 13/14 patients was UIP. The two pathologists correctly diagnosed or refuted UIP in the cryobiopsy specimen in 12/14 cases (85.7%) and 11/14 cases (78.6%), respectively. The level of diagnostic agreement between pathologists was good (kappa 0.59, p = 0.016). Conclusions: Compared to the final explant diagnosis, transbronchial cryobiopsy had high diagnostic accuracy and good inter-observer agreement for UIP pattern. These findings support a potential diagnostic role for cryobiopsy in experienced centers.

Background The global mortality and morbidity rates of bronchiectasis patients due to nontuberculous mycobacteria (NTM) pulmonary infection are on a concerning upward trend. The aims of this study to identify the phenotype of NTM-positive individuals with bronchiectasis. Methods A retrospective single-center observational study was conducted in adult patients with bronchiectasis who underwent bronchoscopy in 2007-2020. Clinical, laboratory, pulmonary function, and radiological data were compared between patients with a positive or negative NTM culture. Results Compared to the NTM-negative group ( n =677), the NTM-positive group ( n =94) was characterized ( P ≤0.05 for all) by older age, greater proportion of females, and higher rates of gastroesophageal reflux disease and muco-active medication use; lower body mass index, serum albumin level, and lymphocyte and eosinophil counts; lower values of forced expiratory volume in one second, forced vital capacity, and their ratio, and lower diffusing lung capacity for carbon monoxide; higher rates of bronchiectasis in both lungs and upper lobes and higher number of involved lobes; and more exacerbations in the year prior bronchoscopy. On multivariate analysis, older age (OR 1.05, 95% CI 1.02-1.07, P =0.001), lower body mass index (OR 1.16, 95% CI 1.16-1.07, P <0.001), and increased number of involved lobes (OR 1.26, 95% CI 1.01-1.44, P =0.04) were associated with NTM infection. Conclusions Patients with bronchiectasis and NTM pulmonary infection are more likely to be older and female with more severe clinical, laboratory, pulmonary function, and radiological parameters than those without NTM infection. This phenotype can be used for screening patients with suspected NTM disease.

Background Tracheostomy is a commonly performed procedure for patients requiring prolonged mechanical ventilation. It can be performed at the bedside using percutaneous dilatational tracheostomy (PDT) under bronchoscopic guidance (BG), which reduces the need for surgical tracheostomies. The aim of this study was to compare early versus late BG-PDT in terms of complications and survival. Methods This retrospective study included patients who underwent BG-PDT between 2012 and 2022 at the Pulmonary Institute of Rabin Medical Center. Data was collected by reviewing demographic and clinical parameters from electronic medical records, with a minimum follow-up of 24 months after the BG-PDT procedure. Early BG-PDT was defined as a procedure performed within 7 days of intubation and late PDT was performed from day 8 onward. Results A total of 207 BG- PDT procedures were performed between 2012 and 2022, of which 188 patients were included in the final analysis. The mean age of the patients was 69 years, with 57.5% being male. Patients who underwent early BG-PDT were younger (mean age 63 vs. 71, p  < 0.01).The most common indications for PDT were respiratory disorders (47.8%) and neurological disorders (19.1%). Patients in the early PDT group had a median overall hospitalization duration of 14 days post BG-PDT (IQR 21–31), compared to 33.5 days (IQR 26–47) in the late group ( p  < 0.01). The overall 1-year survival rate was 54.3% in the early BG-PDT group versus 30.1% in the late BG-PDT group ( p  = 0.04). The overall 3-year survival for both groups was 24.2%, with 45.4% in the early BG-PDT group and 19.6% in the late BG-PDT group ( p  = 0.008). Younger age was found to correlate better survival (OR 1.05, 95% CI: 1.02–1.08, p  < 0.001) and a higher one-year (54.3% vs. 30%, p  = 0.04) and 3-year survival rate of 45.4% in the early vs. 19.6% in the late ( p  = 0.008). Conclusions Bronchoscopy guided percutaneous dilatational tracheostomy is associated with shorter hospitalization duration and has possible survival advantages when performed within 7 days of intubation.

Background Capnography waveform contains essential information regarding physiological characteristics of the airway and thus indicative of the level of airway obstruction. Our aim was to develop a capnography-based, point-of-care tool that can estimate the level of obstruction in patients with asthma and COPD. Methods Two prospective observational studies conducted between September 2016 and May 2018 at Rabin Medical Center, Israel, included healthy, asthma and COPD patient groups. Each patient underwent spirometry test and continuous capnography, as part of, either methacholine challenge test for asthma diagnosis or bronchodilator reversibility test for asthma and COPD routine evaluation. Continuous capnography signal, divided into single breaths waveforms, were analyzed to identify waveform features, to create a predictive model for FEV1 using an artificial neural network. The gold standard for comparison was FEV1 measured with spirometry. Measurements and main results Overall 160 patients analyzed. Model prediction included 32/88 waveform features and three demographic features (age, gender and height). The model showed excellent correlation with FEV1 (R = 0.84), R 2 achieved was 0.7 with mean square error of 0.13. Conclusion In this study we have developed a model to evaluate FEV1 in asthma and COPD patients. Using this model, as a point-of-care tool, we can evaluate the airway obstruction level without reliance on patient cooperation. Moreover, continuous FEV1 monitoring can identify disease fluctuations, response to treatment and guide therapy. Trial registration clinical trials.gov, NCT02805114. Registered 17 June 2016, https://clinicaltrials.gov/ct2/show/NCT02805114

There is no clear evidence whether pirfenidone has a benefit in patients with probable or possible UIP, i.e. when idiopathic pulmonary fibrosis (IPF) is diagnosed with a lower degree of diagnostic certainty. We report on outcomes of treatment with pirfenidone in IPF patients diagnosed with various degrees of certainty. We followed patients in the multi-national European MultiPartner IPF Registry (EMPIRE) first seen between 2015 and 2018. Patients were assessed with HRCT, histopathology and received a multi-disciplinary team (MDT) IPF diagnosis. Endpoints of interest were overall survival (OS), progression-free survival (PFS) and lung function decline. A total of 1626 patients were analysed, treated with either pirfenidone (N = 808) or receiving no antifibrotic treatment (N = 818). When patients treated with pirfenidone were compared to patients not receiving antifibrotic treatment, OS (one-, two- and three-year probability of survival 0.871 vs 0.798; 0.728 vs 0.632; 0.579 vs 0.556, P = 0.002), and PFS (one-, two- and three-year probability of survival 0.597 vs 0.536; 0.309 vs 0.281; 0.158 vs 0.148, P = 0.043) was higher, and FVC decline smaller (-0.073 l/yr vs -0.169 l/yr, P = 0.017). The benefit of pirfenidone on OS and PFS was also seen in patients with probable or possible IPF. This EMPIRE analysis confirms the favourable outcomes observed for pirfenidone treatment in patients with definitive IPF and indicates benefits also for patients with probable or possible IPF.

Background Dexmedetomidine (DEX), is a highly selective alpha2 adrenoceptor (α2-AR) agonist, successfully used in various procedures including flexible bronchoscopy. Randomized controlled trials (RCTs) evaluating DEX sedation during bronchoscopy report equivocal results regarding respiratory and hemodynamic outcomes. Methods We conducted an RCT to evaluate the efficacy and safety of dexmedetomidine compared to propofol for sedation during bronchoscopy. The primary outcome was the number of desaturation events, secondary outcomes were transcutaneous Pco2 level, hemodynamic adverse events and physician and patient satisfaction. Results Overall, 63 patients were included, 30 and 33 in the DEX and propofol groups, respectively. The number of desaturation events was similar between groups, median (IQR) 1 (0–1) and 1 (0–2) in the DEX and control groups, respectively (P = 0.29). Median desaturation time was 1 (0–2) and 1 (0–3) minutes in the DEX and control groups, respectively (P = 0.48). Adverse events included hypotension, 33% vs 21.1% in intervention and control groups, respectively (P = 0.04), bradycardia, cough, and delayed recovery from sedation. Total adverse events were 22 and 7 in DEX and propofol groups, respectively (P = 0.009). Conclusion Dexmedetomidine sedation during bronchoscopy did not show differences in oxygen saturation and transcutaneous CO2 level in comparison to propofol. Moreover, DEX sedation required a significantly higher number of rescue boluses, due to inadequate sedation and was associated with a higher rate of adverse events. Trial registration NCT04211298, registration date: 26.12.2019.

Background: End-stage renal disease (ESRD) affects up to 25% of lung transplant recipients within 10 years. The selection process for kidney transplantation versus dialysis reflects complex clinical decision-making that has not been systematically characterized. Methods: This retrospective observational study analyzed all lung transplant recipients who developed ESRD at our center from 2010 to 2024 (n=32), comparing those receiving kidney transplantation (n = 18) versus those remaining on dialysis (n = 14). We developed an exploratory Clinical Selection Score to retrospectively characterize observed selection patterns and calculated E-values to assess robustness to unmeasured confounding. Results: Kidney transplant recipients were younger (35.7 ± 12.9 vs. 48.4 ± 14.8 years, p = 0.013) with better selection characteristics quantified by our Clinical Selection Score (4.1 ± 0.8 vs. 1.6 ± 1.1 points, p < 0.001). The score showed excellent discrimination (C-statistic 0.82). Living donors were available for 88.9% of transplanted patients versus 0% of dialysis patients. In our selected cohorts, mortality was 22.2% in kidney transplant recipients vs. 78.6% in dialysis patients (p = 0.002), with median survival of 161.6 vs. 126.6 months (p = 0.021). After adjustment for age, kidney transplantation was observed to be associated with 72% lower mortality risk (HR 0.28, 95% CI 0.09–0.89, p = 0.031), though selection bias limits causal interpretation. The E-value of 6.61 suggests robustness to unmeasured confounding. Conclusions: This observational study describes real-world selection patterns and their associated outcomes in lung transplant recipients with ESRD. While carefully selected patients receiving kidney transplantation experienced favorable results, many patients were appropriately managed with dialysis based on medical and non-medical factors. Our analysis provides transparency about selection criteria and outcomes to inform clinical decision-making. Larger multicenter studies are needed to validate these findings and develop prediction tools.

Background Pulmonary alveolar proteinosis (PAP) presents a significant challenge due to its progressive and potentially fatal nature. Whole lung lavage (WLL) is a key treatment for primary PAP with respiratory failure. Despite its efficacy, the lack of standardised protocols has led to diverse practice techniques across different institutions. Our study introduces a novel approach, employing a cardiopulmonary bypass (CPB) system for infusing lavage fluid, a method not previously utilised. This paper will share our pioneering experience with this technique at a tertiary referral centre, focusing on its implementation and safety profile. Methods This retrospective study included patients aged ≥ 18 who underwent WLL for PAP or silicosis. Pre-lavage preparations included chest X-rays and pulmonary function tests (PFT). Preprocedural empiric antibiotics were administered. During lavage, warm saline was infused using a CPB, with cycles of normal saline infusion and degassing until fluid clarity was reached. Positioning techniques facilitated saline drainage. The procedure concluded with intravenous furosemide administration. Results Fifty-two WLLs were identified between 2010 and 2024; complete data was available for 33 procedures. Of these, 91% were due to PAP, and 9% to silicosis. Almost half of the patients did not require additional WLL, while 43% needed sequential contralateral WLL. Median operative and mechanical ventilation times were 65 [58.5, 67.5] and 118 [97, 195] minutes, respectively. The median length of hospital stay was two days [2, 3]. Although not statistically significant, O2 saturation and a 6-minute walk distance increase were observed after the WLL. Conclusion This study outlines our novel approach to WLL, which incorporates rapid saline infusion via a CPB system. Our findings indicate reduced procedure time while maintaining safety and efficacy for treating PAP and silicosis. Despite promising results, the retrospective design and small sample size limit generalizability. Further high-quality studies are warranted to validate and refine this technique.