Reversed halo sign as a radiological feature of tuberculosis - Report of two cases.

Reversed halo sign (RHS) is a radiological feature described as a focal, rounded area of ground-glass opacity surrounded by a ring of consolidation. In this report we describe two unique radiological cases demonstrating diffuse bilateral infiltrates with multiple RHSs in chest CT scans. Both patients were ultimately diagnosed as having tuberculosis (TB) and had been exposed to silica in the past. This report presents for the first time an association between silica exposure and RHS on CT scans among TB patients. It highlights the importance of having a high index of suspicion for TB in similar scenarios.

Pretransplant NT-proBNP levels are associated with mortality among lung transplant recipients.

The prognostic significance of pretransplant N-terminal pro-brain (B)-type natriuretic peptide (NT-proBNP) level has not been investigated in lung transplant recipients. The electronic files of 173 patients with chronic lung disease who underwent lung transplantation in 2018-2022 at a tertiary medical center were retrospectively reviewed. Right heart catheterization (RHC) and NT-proBNP determination were performed preoperatively in all cases. Pretransplant demographic, clinical, and laboratory data were compared between posttransplant survivors and nonsurvivors. Correlations of NT-proBNP values with lung function and RHC parameters and all-cause mortality were analyzed. NT-proBNP level correlated positively with mean pulmonary artery pressure (R = 0.51, p < 0.001) and pulmonary vascular resistance (PVR) (R = 0.45, p = 0.0013), and negatively with diffusing lung capacity for carbon monoxide (R = -0.25, p = 0.0017), cardiac index (R = -0.26, p = 0.001), and cardiac output (R = -0.23, p = 0.004). Over a median follow-up time of 23.22 months, 74 patients died. On univariate analysis, mortality was significantly associated with higher log-NT-proBNP (hazard ratio [HR] = 0.54, 95% confidence interval [CI] 1.15-2.05, p = 0.016), older age at transplant registration (HR = 1.033, 95% CI 1.009-1.058, p = 0.0068), higher PVR (HR 1.15, 95% CI 1.07-1.23, p = 0.015), and lower cardiac output (HR = 0.62, 95% CI 0.42-0.92, p = 0.045). On multivariate analysis adjusted for age, sex, and body mass index, mortality significance was maintained only for higher log-NT-proBNP (HR = 1.54, 95% CI 1.12-2.11, p = 0.007). Among lung transplant recipients, pretransplant NT-proBNP levels correlated well with RHC parameters and were strongly associated with posttransplantation mortality. Assessment of NT-proBNP may improve risk stratification of lung transplant candidates.

Phenotypical characteristics of nontuberculous mycobacterial infection in patients with bronchiectasis.

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.

High antinuclear antibody titer is associated with increased mortality risk in patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a diagnosis of exclusion, requiring that potential etiologies of interstitial lung disease be ruled out. Antinuclear antibody (ANA) testing is commonly performed in individuals with IPF, but the clinical significance of ANA positivity remains uncertain. A retrospective search identified 161 patients diagnosed with IPF between May 2010 and January 2021. Data on ANA titers at the time of diagnosis were available in all cases. Mean age of the patients was 66.4 ± 9.6 years; 70.8% were male. ANA titers were high (≥ 1:160) in 25.4% of the cohort. Baseline characteristics were comparable between those with high and low ANA titers. During follow-up (median 28 months), 93 patients (57%) died. On Cox proportional-hazards analysis with lung transplantation entered as a competing risk and adjusting for potential confounders (age, sex, and baseline forced vital capacity and diffusing lung capacity for carbon monoxide), ANA ≥ 1:160, as a dichotomized variable, was significantly associated with case-specific mortality (HR 2.25, 95% CI 1.14-4.42, P = 0.02) and older age (for each 10-year increment, HR 1.55, 95% CI 1.07-2.25, P = 0.02). High ANA titers appear to be associated with increased mortality in IPF. This finding emphasizes the potential prognostic value of ANA testing. Further studies are needed to validate these findings and explore their implications for patient management.

The acute effect of inhaled nitric oxide on the exercise capacity of patients with advanced interstitial lung disease: a randomized controlled trial.

BACKGROUND: Inhaled nitric oxide (iNO) selectively acts on the pulmonary vasculature of ventilated lung tissue by reducing pulmonary vascular resistance and intrapulmonary shunt. This effect may reduce ventilation/perfusion mismatch and decrease pulmonary hypertension in patients with interstitial lung disease. METHODS: In a prospective, single-blinded, randomized, placebo-controlled trial, participants with advanced interstitial lung disease, underwent two separate six-minute walk tests (6MWT): one with iNO and the other with a placebo. The primary outcome measured the difference in meters between the distances covered in the two tests. Secondary outcomes included oxygen saturation levels, distance-saturation product, and Borg dyspnea score. A predefined subgroup analysis was conducted for patients with pulmonary hypertension. RESULTS: Overall, 44 patients were included in the final analysis. The 6MWT distance was similar for iNO treatment and placebo, median 362 m (IQR 265-409) vs 371 m (IQR 250-407), respectively (p = 0.29). Subgroup analysis for patients with pulmonary hypertension showed no difference in 6MWT distance with iNO and placebo, median 339 (256-402) vs 332 (238-403) for the iNO and placebo tests respectively (P=0.50). No correlation was observed between mean pulmonary artery pressure values and the change in 6MWT distance with iNO versus placebo (spearman correlation Coefficient 0.24, P=0.33). CONCLUSION: In patients with advanced interstitial lung disease, both with and without concurrent pulmonary hypertension, the administration of inhaled nitric oxide failed to elicit beneficial effects on the six-minute walk distance and oxygen saturation. The use of inhaled NO was found to be safe and did not lead to any serious side effects. TRIAL REGISTRATION: (NCT03873298, MOH_2018-04-24_002331).

Cardiopulmonary Exercise Testing Provides Prognostic Information in Advanced Cystic Fibrosis Lung Disease.

Rationale: Cardiopulmonary exercise testing (CPET) provides prognostic information in cystic fibrosis (CF); however, its prognostic value for patients with advanced CF lung disease is unknown. Objectives: To determine the prognostic value of CPET on the risk of death or lung transplant (LTX) within 2 years. Methods: We retrospectively collected data from 20 CF centers in Asia, Australia, Europe, and North America on patients with a forced expiratory volume in 1 second (FEV1) ⩽ 40% predicted who performed a cycle ergometer CPET between January 2008 and December 2017. Time to death/LTX was analyzed using mixed Cox proportional hazards regression. Conditional inference trees were modeled to identify subgroups with increased risk of death/LTX. Results: In total, 174 patients (FEV1, 30.9% ± 5.8% predicted) were included. Forty-four patients (25.5%) died or underwent LTX. Cox regression analysis adjusted for age, sex, and FEV1 revealed percentage predicted peak oxygen uptake ([Formula: see text]o2peak) and peak work rate (Wpeak) as significant predictors of death/LTX: adjusted hazard ratios per each additional 10% predicted were 0.60 (95% confidence interval, 0.43-0.90; P = 0.008) and 0.60 (0.48-0.82; P < 0.001). Tree-structured regression models, including a set of 11 prognostic factors for survival, identified Wpeak to be most strongly associated with 2-year risk of death/LTX. Probability of death/LTX was 45.2% for those with a Wpeak ⩽ 49.2% predicted versus 10.9% for those with a Wpeak > 49.2% predicted (P < 0.001). Conclusions: CPET provides prognostic information in advanced CF lung disease, and Wpeak appears to be a promising marker for LTX referral and candidate selection.

The Impact of Switching to a Second Antifibrotic in Patients With Idiopathic Pulmonary Fibrosis: A Retrospective Multicentre Study From the EMPIRE Registry.

INTRODUCTION: Most patients with idiopathic pulmonary fibrosis (IPF) treated with antifibrotics (AF) have progressive disease despite treatment. A switch of AF may improve survival, but evidence from randomised controlled trials is missing. We aimed to evaluate the efficacy of an AF switch on survival and FVC decline in patients from the European MultiPartner IPF registry (EMPIRE). METHODS: The study included 612 patients who discontinued the first antifibrotic therapy. Patients were grouped and analysed from two perspectives: (1) whether they had received a second antifibrotic treatment after the discontinuation of the first therapy, and (2) a reason for discontinuation of the first AF - "lack of efficacy" (LE) and "intolerance" (INT). RESULTS: While 263 (43%) of 612 patients received no second AF ("non-switched"), 349 (57%) patients switched. Overall survival was higher in patients who received a second AF (median 50 vs. 29 months; adjusted HR 0.64, P=0.023). Similarly, the annual FVC decline was significantly reduced in switched patients: -98ml/y in switched and -172ml/y in non-switched patients (P=0.023), respectively. The switched patients had similar risk for mortality in both LE and INT groups (adjusted HR 0.95, P=0.85). The high impact of switching on survival was demonstrated in LE patients (adjusted HR 0.27, P<0.001). CONCLUSION: The patients without a second AF had significantly shorter overall survival. Our analysis suggests the importance of switching patients with an ineffective first AF therapy to a second AF therapy.

Endobronchial closure of broncho-biliary fistula using Amplatzer device: Case report.

Broncho-biliary fistula (BBF) is an extremely rare but serious medical condition resulting from pathological communication between the biliary system and the bronchial tree. Treatment options include both surgical and non-surgical approaches. Several endobronchial techniques, such as the spigot and glue, can be used for this purpose. This report discusses a patient who developed a broncho-biliary fistula following a liver biopsy. The BBF was diagnosed during bronchoscopy and successfully treated with an endobronchial Amplatzer device. To the best of our knowledge, this is the first report of the use of the Amplatzer device to manage BBF.

A single center Israeli experience in pregnancy post lung transplantation: Feasibility of successful two or more full-term pregnancies in individual lung transplant recipients.

INTRODUCTION: Female lung transplant recipients (LTRs) of reproductive age are increasingly considering pregnancy due to advances in post-transplant management and improved survival. We report our experience with pregnancy in LTRs, with an emphasis on two or more successful full-term pregnancies in individual transplant recipients. METHODS: We conducted a retrospective analysis of pregnancies in LTRs at our transplant center and collected maternal and fetal outcomes. RESULTS: In our patient cohort, eight female LTRs conceived a total of 17 pregnancies, resulting in 13 newborns, 12 at full term, and 11 with a birth weight > 2.5 kg. Three of the LTRs had two or more successful full-term pregnancies. LTRs required a significant tacrolimus dose increase to maintain target trough levels during pregnancy. Six recipients are currently clinically stable and active, three with lung function comparable to pre-pregnancy values, and three with evidence of chronic lung allograft dysfunction (CLAD), but stable lung function. Two of the eight LTRs died subsequent to childbirth secondary to chronic respiratory failure due to CLAD, at a mean of 11 years post-transplantation and a mean of 4.5 years after childbirth. CONCLUSION: Pregnancy following lung transplantation is feasible and can be achieved with acceptable maternal and newborn outcomes. Importantly, LTRs can successfully have two or more full-term pregnancies.

Bronchoscopy for management and identification of etiology of right middle lobe syndrome: Analysis of 66 cases.

BACKGROUND: Right middle lobe (RML) syndrome is a recurrent or chronic obstruction of the RML causing atelectasis of the right middle lobe due to mechanical and nonmechanical etiologies. The consequences of untreated RML syndrome range from chronic cough to post-obstructive pneumonia and bronchiectasis. We report here our bronchoscopy experience in patients with RML syndrome. METHODS: We conducted a retrospective study of adult patients who underwent bronchoscopy for RML syndrome at Rabin Medical Center from 2008 through 2022. Demographic data and medical history, bronchoscopy findings and procedures, and follow-up results were collected. RESULTS: A total of 66 patients (57.6% male, mean age 63 ± 13 years) underwent bronchoscopy for RML syndrome during the study period. Bronchoscopy revealed a mechanical etiology in 49 (74.2%) cases, including endobronchial mass (21, 31.8%) and external compression (7, 10.6%). Malignancy was identified in 20 (30.3%) cases. In 62 patients (93.9%), the bronchoscopy resulted in partial or complete reopening of the RML bronchus. The therapeutic bronchoscopic procedures were balloon dilatation (19), laser ablation (17), mechanical debridement (12), endobronchial stent insertion (11), and cryoablation (6). CONCLUSIONS: Malignancy was identified as the etiology of RML syndrome in approximately 25% of cases, suggesting bronchoscopy should be performed in every case of RML atelectasis. To our knowledge, this is the first reported series of endobronchial stenting of the RML bronchus in the context of RML syndrome.

Amplatzer Occluders for Effective Nonsurgical Management of Bronchopleural Fistulae.

BACKGROUND: To assess the safety and efficacy of bronchopleural fistulae closure with Amplatzer occluder devices (AGA Medical, Golden Valley, MN) through our experience of over 14 years. METHODS: Retrospective data review of patients from Rabin Medical Center who underwent Amplatzer occluder device placement between March 2007 and September 2021 for bronchopleural fistulae closure. RESULTS: In total, 72 patients had 83 Amplatzer occluder devices implanted for bronchopleural fistulae closure. The median age was 65.5 (interquartile range 56.0-72.3) years. The primary diseases were lung malignancy (48 [66.7%]) and thoracic infection (9 [12.5%]). Bronchopleural fistulae developed mainly following pneumonectomy (40.3%) and lobectomy (33.3%), with a median time from surgery to Amplatzer placement of 3.9 (interquartile range 1.4-16.4) months. We encountered no procedural or immediate postprocedural complications or deaths. Six months after Amplatzer insertion, there were 7 (8.4%) Amplatzer removals and 11 (15.3%) fistula-related deaths. CONCLUSIONS: Amplatzer occluders are a safe modality for nonsurgical bronchopleural fistulae management with ease of placement under moderate sedation and flexible bronchoscopy with good short- and long-term effectivity.

Immunogenicity of a Third Dose of BNT162b2 Vaccine among Lung Transplant Recipients-A Prospective Cohort Study.

Two doses of mRNA SARS-CoV-2 vaccines elicit an attenuated humoral immune response among immunocompromised patients. Our study aimed to assess the immunogenicity of a third dose of the BNT162b2 vaccine among lung transplant recipients (LTRs). We prospectively evaluated the humoral response by measuring anti-spike SARS-CoV-2 and neutralizing antibodies in 139 vaccinated LTRs ~4-6 weeks following the third vaccine dose. The t-cell response was evaluated by IFNγ assay. The primary outcome was the seropositivity rate following the third vaccine dose. Secondary outcomes included: positive neutralizing antibody and cellular immune response rate, adverse events, and COVID-19 infections. Results were compared to a control group of 41 healthcare workers. Among LTRs, 42.4% had a seropositive antibody titer, and 17.2% had a positive t-cell response. Seropositivity was associated with younger age (t = 3.736, p < 0.001), higher GFR (t = 2.355, p = 0.011), and longer duration from transplantation (t = -1.992, p = 0.024). Antibody titer positively correlated with neutralizing antibodies (r = 0.955, p < 0.001). The current study may suggest the enhancement of immunogenicity by using booster doses. Since monoclonal antibodies have limited effectiveness against prevalent sub-variants and LTRs are prone to severe COVID-19 morbidity, vaccination remains crucial for this vulnerable population.

[INTUBATION RELATED TRACHEAL RUPTURE: EXPECTING THE UNEXPECTED].

INTRODUCTION: This case involved a 67-year-old female who was admitted for general anesthesia for a mitral clip procedure. Following anesthesia induction, the patient underwent an uneventful orotracheal intubation. Shortly afterwards she developed an ongoing respiratory failure, accompanied by neck and chest subcutaneous emphysema. Upon workup, she was found to have a 6 cm long tracheal laceration on the posterior side. Emergency repair surgery was performed using an extracorporeal membrane oxygenator (ECMO). The patient passed away 11 days later from sepsis. The aim of this case report is to increase awareness of this rare intubation complication, and explore the best approach to prevent, diagnose and treat tracheal injuries during endotracheal intubation.

Lung Transplantation for Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation: A Single-center Experience.

BACKGROUND: Late-onset pulmonary complications can occur following hematological stem cell transplantation (HSCT). In allogeneic HSCT these complications are often associated with chronic graft-versus-host disease (GVHD). Lung transplantation (LTx) often remains the only viable therapeutic option in these patients. OBJECTIVES: To describe our experience with LTx due to GVHD after HSCT and to compare the long-term survival of this group of patients to the overall survival of our cohort of LTx recipients for other indications. METHODS: We retrospectively retrieved all data on patients who had undergone LTx for end-stage lung disease as a sequela of allogeneic HSCT, between 1997 and 2021, at Rabin Medical Center in Israel. RESULTS: A total of 15 of 850 patients (1.7%) from our cohort of LTx recipients fulfilled the criteria of LTx as a sequela of late pulmonary complication after allogeneic HSCT. The median age at the time of HSCT was 33 years (median 15-53, range 3-60). The median time between HSCT and first signs of chronic pulmonary GVHD was 24 months (interquartile range [IQR] 12-80). The median time from HSCT to LTx was 96 months (IQR 63-120). Multivariate analysis showed that patients transplanted due to GVHD had similar survival compared to patients who were transplanted for other indications. CONCLUSIONS: LTx for GVHD after allogeneic HSCT constitutes an important treatment strategy. The overall survival appears to be comparable to patients after LTx for other indications.

Prognostic Significance of the N-Terminal Pro-B-Type Natriuretic Peptide in Lung Transplant Candidates on the Waiting List.

We investigated the prognostic significance of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in lung transplant candidates, in a retrospective single-center study. Data regarding various baseline characteristics and all-cause mortality were collected for 205 lung transplant candidates placed on waitlist for transplantation from November 2017 to December 2019. Associations of NT-proBNP levels with baseline characteristics and mortality were analyzed. Results showed NT-proBNP values correlated positively with age, forced vital capacity, mean pulmonary artery pressure (MPAP), and pulmonary capillary wedge pressure; and negatively with diffusing lung capacity for carbon monoxide and cardiac index. The optimal cut-off of NT-proBNP for predicting MPAP levels > 35 mmHg was 251 pg/mL; with 58.1% sensitivity, 85.7% specificity, 45.0% positive predictive value, and 91.0% negative predictive value. During a median follow-up period of 2.2 years, 97 patients underwent lung transplantation, 42 died waiting for donation, and 66 were alive and still waiting for transplantations. On multivariate analysis, higher NT-proBNP levels were strongly associated with increased mortality among waitlisted lung transplant candidates (HR 1.49, 95% CI 1.10−2.03, p = 0.01). In conclusion NT-proBNP can predict mortality among waitlisted lung transplant candidates. Lower levels of NT-proBNP can preclude severe pulmonary artery hypertension. Assessment of NT-proBNP may improve risk stratification among lung transplant candidates.

Survival and lung function decline in patients with definite, probable and possible idiopathic pulmonary fibrosis treated with pirfenidone.

BACKGROUND: 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. METHODS AND FINDINGS: 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. RESULTS: 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. CONCLUSIONS: 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.