Patients with COVID-19 report severe respiratory symptoms consistent with ARDS. The clinical presentation of ARDS in COVID-19 is often atypical, as patients with COVID-19 exhibit a disproportionate ...hypoxemia compared with relatively preserved lung mechanics. This pattern is more similar to neonatal respiratory distress syndrome secondary to surfactant deficiency, which has been shown to benefit from exogenous surfactant. We present our experience with exogenous surfactant treatment in a patient with COVID-19 experiencing COVID-19-related ARDS. The patient responded with improved oxygenation, and we believe surfactant was the catalyst for the successful extubation and clinical improvement of the patient.
Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized by progressive surfactant accumulation and hypoxemia. It is caused by disruption of granulocyte-macrophage ...colony-stimulating factor (GM-CSF) signaling, which pulmonary alveolar macrophages require to clear surfactant. Recently, inhaled GM-CSF was shown to improve the partial pressure of arterial oxygen in patients with aPAP.
In a double-blind, placebo-controlled, three-group trial, we randomly assigned patients with aPAP to receive the recombinant GM-CSF molgramostim (300 μg once daily by inhalation), either continuously or intermittently (every other week), or matching placebo. The 24-week intervention period was followed by an open-label treatment-extension period. The primary end point was the change from baseline in the alveolar-arterial difference in oxygen concentration (A-aDo
) at week 24.
In total, 138 patients underwent randomization; 46 were assigned to receive continuous molgramostim, 45 to receive intermittent molgramostim, and 47 to receive placebo. Invalid A-aDo
data for 4 patients (1 in each molgramostim group and 2 in the placebo group) who received nasal oxygen therapy during arterial blood gas measurement were replaced by means of imputation. For the primary end point - the change from baseline in the A-aDo
at week 24 - improvement was greater among patients receiving continuous molgramostim than among those receiving placebo (-12.8 mm Hg vs. -6.6 mm Hg; estimated treatment difference, -6.2 mm Hg; P = 0.03 by comparison of least-squares means). Patients receiving continuous molgramostim also had greater improvement than those receiving placebo for secondary end points, including the change from baseline in the St. George's Respiratory Questionnaire total score at week 24 (-12.4 points vs. -5.1 points; estimated treatment difference, -7.4 points; P = 0.01 by comparison of least-squares means). For multiple end points, improvement was greater with continuous molgramostim than with intermittent molgramostim. The percentages of patients with adverse events and serious adverse events were similar in the three groups, except for the percentage of patients with chest pain, which was higher in the continuous-molgramostim group.
In patients with aPAP, daily administration of inhaled molgramostim resulted in greater improvements in pulmonary gas transfer and functional health status than placebo, with similar rates of adverse events. (Funded by Savara Pharmaceuticals; IMPALA ClinicalTrials.gov number, NCT02702180.).
A major barrier to chronic obstructive pulmonary disease (COPD) research and management is lack of easily obtained biomarkers that are predictive of clinically important outcome measures.
We sought ...to investigate in patients admitted for acute exacerbation of COPD (AECOPD) the association of D-dimer (fibrin degradation product) obtained upon admission with in-hospital mortality and postdischarge prognosis.
Clinical and laboratory data were evaluated in 61 patients admitted for AECOPD in whom D-dimer levels were obtained and in whom venous thromboembolism/pulmonary embolism was excluded. Receiver operating characteristics curve was used to determine the optimal cutoff level for D-dimer that discriminated survivors versus nonsurvivors during index hospitalization, and during follow-up that extended to a median observation period of 62.6 months.
Mean (± SD) age of the study cohort was 71.2 ± 10.5 years. Mean D-dimer level in nonsurvivors (n = 12) was significantly higher than in survivors (n = 49): 3.18 ± 0.97 mg/L versus 1.45 ± 1.18 mg/L, respectively, P = 0.0006. D-dimer level >1.52 mg/L predicted in-hospital mortality with a sensitivity and specificity of 100% and 63.6%, respectively. After discharge, median survival of patients with D-dimer above and below 1.52 mg/L were 9.6 and 62.6 months, respectively (hazard ratio = 2.636; 95% confidence interval = 1.271-6.426, P = 0.0111).
Elevated D-dimer is a reliable prognostic marker for both short-term and long-term survival in patients admitted for AECOPD. Prospective studies are required to further establish the appropriate role of D-dimer as a prognostic biomarker in patients with COPD.
Abstract Background Combination therapy (CT) for patients with pulmonary arterial hypertension (PAH) has been recommended for many years, despite weak evidence of efficacy over monotherapy (MT). A ...previous meta-analysis comparing CT vs MT with pulmonary vasodilators failed to demonstrate a clear reduction in clinical worsening events. Methods We searched for relevant articles in PubMed, EMBASE, the Cochrane Database, and clinicaltrials.gov ; we also manually searched review articles and conference abstracts from 1980-December 2015. Target articles were double-blinded studies of 2 or more pulmonary vasodilators given in combination vs monotherapy for treatment of patients with PAH. The principal outcome of interest was “combined clinical worsening” (CCW) events (including but not limited to death or hospitalization). Data on physiological outcomes were also explored. Meta-analysis was performed using the DerSimonian and Laird random-effects model. Results We extracted data from 18 randomized controlled trials (RCTs) (N = 4162). CT was associated with a significant 38% reduction of risk of CCW (15 RCTs: n = 3906; risk ratio RR, 0.62; 95% confidence interval CI, 0.50-0.77). This reduction in risk was driven by a reduction in nonfatal end points (12 RCTs: n = 2611; RR, 0.56; 95% CI, 0.40-0.78) and not by a reduction of mortality (12 RCTs: n = 2717; RR, 0.79; 95% CI, 0.53-1.17). CT was also associated with improvement in 6-minute walking distance (10 RCTs: n = 1553; weighted mean difference WMD, +23.0 m; 95% CI, 15.9-30.1), improved functional class (9 RCTs: n = 1737; RR, 1.26; 95% CI, 1.05-1.51), and beneficial effects on pulmonary hemodynamics such as cardiac index (WMD, +0.35 L/min/m; 95% CI, 0.14-0.56). Conclusions In this highly comprehensive meta-analysis, CT reduces the risk of CCW events in patients with PAH and brings physiological improvement.
Aims
To assess the short‐term immunogenicity to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) mRNA vaccine in a population of heart transplant (HTx) recipients. A prospective ...single‐centre cohort study of HTx recipients who received a two‐dose SARS‐CoV‐2 mRNA vaccine (BNT162b2, Pfizer‐BioNTech).
Methods and results
Whole blood for anti‐spike IgG (S‐IgG) antibodies was drawn at days 21–26 and at days 35–40 after the first vaccine dose. Geometric mean titres (GMT) ≥50 AU/mL were interpreted positive. Included were 42 HTx recipients at a median age of 61 interquartile range (IQR) 44–69 years. Median time from HTx to the first vaccine dose was 9.1 (IQR 2.6–14) years. Only 15% of HTx recipients demonstrated the presence of positive S‐IgG antibody titres in response to the first vaccine dose GMT 90 (IQR 54–229) AU/mL. Overall, 49% of HTx recipients induced S‐IgG antibodies in response to either the first or the full two‐dose vaccine schedule GMT 426 (IQR 106–884) AU/mL. Older age 68 (IQR 59–70) years vs. 46 (IQR 34–63) years, P = 0.034 and anti‐metabolite‐based immunosuppression protocols (89% vs. 44%, P = 0.011) were associated with low immunogenicity. Importantly, 36% of HTx recipients who were non‐responders to the first vaccine dose became S‐IgG seropositive in response to the second vaccine dose. Approximately a half of HTx recipients did not generate S‐IgG antibodies following SARS‐CoV‐2 two‐dose vaccine.
Conclusions
The generally achieved protection from SARS‐CoV‐2 mRNA vaccination should be regarded with caution in the population of HTx recipients. The possible benefit of additive vaccine should be further studied.
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.
Background
Mucormycosis is a rare infection in lung transplant recipients (LTR). Our objective was to better define the clinical presentation and optimal management of this frequently lethal ...infection.
Methods
A systematic review of the literature was performed to identify all published cases of mucormycosis in LTR using PubMed/MEDLINE. These cases were analyzed together with a new case series from our clinic.
Results
Literature search yielded 44 articles matching the inclusion criteria, describing 121 cases. Six additional cases were identified from our clinic. Data regarding infection site and outcome were available for a total of 53 patients. The lungs were the most common site of infection (62%), followed by rhinocerebral and disseminated disease. Most cases (78%) developed in the first post‐transplant year, with over 40% of them in the first month. Additional risk factors for mucormycosis were identified in over half of the patients. Surgical debridement was uncommon in pulmonary infection (9%). Posaconazole therapy was used in 35% of cases, mostly in combination with amphotericin B. Overall mortality was 32% but varied according to site of infection.
Conclusion
Mucormycosis in LTRs tends to be an early post‐surgical infection, associated with additional risk factors and intensified immunosuppressive states, and most often affects the lungs, where surgical debridement is rarely feasible. Posaconazole as first‐line therapy should be further explored.
Abstract 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.
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