Low-field MRI lung opacity severity associated with decreased DLCO in post-acute Covid-19 patients.

OBJECTIVES: To evaluate the clinical significance of low-field MRI lung opacity severity. METHODS: Retrospective cross-sectional analysis of post-acute Covid-19 patients imaged with low-field MRI from 9/2020 through 9/2022, and within 1 month of pulmonary function tests (PFTs), 6-min walk test (6mWT), and symptom inventory (SI), and/or within 3 months of St. George Respiratory Questionnaire (SGRQ) was performed. Univariate and correlative analyses were performed with Wilcoxon, Chi-square, and Spearman tests. The association between disease and demographic factors and MR opacity severity, PFTs, 6mWT, SI, and SGRQ, and association between MR opacity severity with functional and patient-reported outcomes (PROs), was evaluated with mixed model analysis of variance, covariance and generalized estimating equations. Two-sided 5 % significance level was used, with Bonferroni multiple comparison correction. RESULTS: 81 MRI exams in 62 post-acute Covid-19 patients (median age 57, IQR 41-64; 25 women) were included. Exams were a median of 8 months from initial illness. Univariate analysis showed lung opacity severity was associated with decreased %DLCO (ρ = -0.55, P = .0125), and lung opacity severity quartile was associated with decreased %DLCO, predicted TLC, FVC, and increased FEV1/FVC. Multivariable analysis adjusting for sex, initial disease severity, and interval from Covid-19 diagnosis showed MR lung opacity severity was associated with decreased %DLCO (P < .001). Lung opacity severity was not associated with PROs. CONCLUSION: Low-field MRI lung opacity severity correlated with decreased %DLCO in post-acute Covid-19 patients, but was not associated with PROs.

The impact of gas transfer on responses to exercise training in patients with pulmonary hypertension.

Exercise training is recommended for pulmonary hypertension (PH). Post hoc analysis of the PH and Home-Based (PHAHB) trial stratified patients into two groups based on median diffusing capacity of the lungs for carbon monoxide (DLCO). Patients with higher DLCO had a greater improvement in physical activity performance in response to exercise training, compared to those with lower DLCO. DLCO may be an important consideration in prescribing exercise in PH.

Clinico-radiological and pulmonary function assessment of post-COVID-19 patients with respiratory symptoms.

Background: Respiratory symptoms may persist for several weeks following the initial coronavirus disease 2019 (COVID-19) infection. The aims and objectives were to assess the clinical symptoms, pulmonary functions, and radiological changes and to assess the cardio-vascular complications in post-COVID-19 patients. Methods: This observational study was conducted in the Department of Pulmonary Medicine in collaboration with the Department of Cardiology, SCBMCH, Cuttack, from March 2021 to August 2022 on 75 post-COVID-19 patients with respiratory symptoms from 4 weeks to 2 years after treatment for COVID-19 infection. Post-COVID patients having previous respiratory diseases were excluded from the study. Results: Among 75 patients, the most common age group was 18-30 years with a male-to-female ratio of 2.5:1. Based on O2 requirement, patients were divided into the mild symptomatic group and moderate to severe pneumonia group. The most common respiratory symptom was dyspnea, followed by cough with expectoration. Bilateral crepitations were found in 17% of cases. C-reactive protein (CRP) and D-dimer were increased in 38.6% and 32% of patients, respectively. 42.6% had abnormal chest X-ray, and the most common abnormal finding was reticular thickening. In spirometry, the restrictive pattern and mixed pattern were the predominant types documented in 49.3% and 13.3% of cases, respectively, which were significant in the moderate-severe group. Diffusion capacity of the lungs for carbon monoxide (DLCO) was performed in only 19 patients (mild group 13 and moderate-severe group 6). Twelve (63.2%) patients had abnormal DLCO. P- values were significant for RV (0.0482) and RV/TLC (0.0394). High-resolution computed tomography (HRCT) of the thorax was abnormal in 55.7% with the most common abnormalities as inter- and intra-lobular septal thickening. The left ventricular ejection fraction was preserved in all patients, with right atrium and right ventricle enlargement in 2.6% and pulmonary hypertension in 4.0% of participants. Conclusion: All post-COVID-19 patients having respiratory symptoms after recovery from acute COVID-19 may be referred by family care physicians to a dedicated post-COVID center for further evaluation, management, and early rehabilitation to decrease the morbidity in recovered patients. Persistent increased blood parameters like TLC, N/L ratio, RBS, CRP, and D-dimer seen in recovered post-COVID-19 patients. The long-term impact of CT findings on respiratory symptoms, pulmonary functions, and quality of life is unknown. Cardiovascular abnormalities in post-COVID-19 patients are infrequent.

Socio-economic conditions affect health-related quality of life, during recovery from acute SARS-CoV-2 infection : Results from the VASCO study (VAriabili Socioeconomiche e COVID-19), on the "Surviving-COVID" cohort, from Bergamo (Italy).

BACKGROUND: Recovery from acute COVID-19 may be slow and incomplete: cases of Post-Acute Sequelae of COVID (PASC) are counted in millions, worldwide. We aimed to explore if and how the pre-existing Socio-economic-status (SES) influences such recovery. METHODS: We analyzed a database of 1536 consecutive patients from the first wave of COVID-19 in Italy (February-September 2020), previously admitted to our referral hospital, and followed-up in a dedicated multidisciplinary intervention. We excluded those seen earlier than 12 weeks (the conventional limit for a possible PASC syndrome), and those reporting a serious complication from the acute phase (possibly accounting for symptoms persistence). We studied whether the exposition to disadvantaged SES (estimated through the Italian Institute of Statistics's model - ISTAT 2017) was affecting recovery outcomes, that is: symptoms (composite endpoint, i.e. at least one among: dyspnea, fatigue, myalgia, chest pain or palpitations); Health-Related-Quality-of-Life (HRQoL, as by SF-36 scale); post-traumatic-stress-disorder (as by IES-R scale); and lung structural damage (as by impaired CO diffusion, DLCO). RESULTS: Eight-hundred and twenty-five patients were included in the analysis (median age 59 years; IQR: 50-69 years, 60.2% men), of which 499 (60.5%) were previously admitted to hospital and 27 (3.3%) to Intensive-Care Unit (ICU). Those still complaining of symptoms at follow-up were 337 (40.9%; 95%CI 37.5-42.2%), and 256 had a possible Post-Traumatic Stress Disorder (PTSD) (31%, 95%CI 28.7-35.1%). DLCO was reduced in 147 (19.6%, 95%CI 17.0-22.7%). In a multivariable model, disadvantaged SES was associated with a lower HRQoL, especially for items exploring physical health (Limitations in physical activities: OR = 0.65; 95%CI = 0.47 to 0.89; p = 0.008; AUC = 0.74) and Bodily pain (OR = 0.57; 95%CI = 0.40 to 0.82; p = 0.002; AUC = 0.74). We did not observe any association between SES and the other outcomes. CONCLUSIONS: Recovery after COVID-19 appears to be independently affected by a pre-existent socio-economic disadvantage, and clinical assessment should incorporate SES and HRQoL measurements, along with symptoms. The socioeconomic determinants of SARS-CoV-2 disease are not exclusive of the acute infection: this finding deserves further research and specific interventions.

Hepatopulmonary Syndrome in a Patient With Autoimmune Hepatitis Without Liver Cirrhosis: A Case Report.

Intrapulmonary vasodilation leads to impaired arterial oxygenation, a hallmark of hepatopulmonary syndrome (HPS), a common pulmonary complication in end-stage liver disease. We present a case of HPS primarily diagnosed due to orthodeoxia in a 62-year-old ex-smoker with autoimmune hepatitis, under immunosuppressive treatment, but without liver cirrhosis. The patient reported dyspnea at rest that improved when supine. A recent chest CT scan showed no pulmonary embolism but indicated small nodules, bronchiectasis, and emphysema lesions. Functional breath monitoring revealed a low diffusing capacity for carbon monoxide (48% predicted). Blood gas analysis showed an increased alveolar-arterial difference, and contrast-enhanced echocardiography confirmed HPS with bubbles in the left heart chambers after the fourth cardiac cycle. Lung perfusion scintigraphy was negative for thromboembolic disease, but kidney imaging reinforced the HPS diagnosis. Our case is, to the best of our knowledge, the first presentation of HPS in a patient with autoimmune hepatitis without evidence of liver cirrhosis. This case highlights a rare instance of HPS in a patient with autoimmune hepatitis without liver cirrhosis, where orthodeoxia was the first clinical manifestation.

Extracellular Vesicles Induce Nuclear Factor-κB Activation and Interleukin-8 Synthesis through miRNA-191-5p Contributing to Inflammatory Processes: Potential Implications in the Pathogenesis of Chronic Obstructive Pulmonary Disease.

Extracellular vesicles (EVs) play a pivotal role in a variety of physiologically relevant processes, including lung inflammation. Recent attention has been directed toward EV-derived microRNAs (miRNAs), such as miR-191-5p, particularly in the context of inflammation. Here, we investigated the impact of miR-191-5p-enriched EVs on the activation of NF-κB and the expression of molecules associated with inflammation such as interleukin-8 (IL-8). To this aim, cells of bronchial epithelial origin, 16HBE, were transfected with miR-191-5p mimic and inhibitor and subsequently subjected to stimulations to generate EVs. Then, bronchial epithelial cells were exposed to the obtained EVs to evaluate the activation of NF-κB and IL-8 levels. Additionally, we conducted a preliminary investigation to analyze the expression profiles of miR-191-5p in EVs isolated from the plasma of patients diagnosed with chronic obstructive pulmonary disease (COPD). Our initial findings revealed two significant observations. First, the exposure of bronchial epithelial cells to miR-191-5p-enriched EVs activated the NF-kB signaling and increased the synthesis of IL-8. Second, we discovered the presence of miR-191-5p in peripheral blood-derived EVs from COPD patients and noted a correlation between miR-191-5p levels and inflammatory and functional parameters. Collectively, these data corroborate and further expand the proinflammatory role of EVs, with a specific emphasis on miR-191-5p as a key cargo involved in this process. Consequently, we propose a model in which miR-191-5p, carried by EVs, plays a role in airway inflammation and may contribute to the pathogenesis of COPD.

Unveiling Silent Consequences: Impact of Pulmonary Tuberculosis on Lung Health and Functional Wellbeing after Treatment.

Background: Pulmonary tuberculosis (TB) remains a major public health issue in India, with high incidence and mortality. The current literature on post-TB sequelae functional defects focuses heavily on spirometry, with conflicting obstruction vs. restriction data, lacks advanced statistical analysis, and has insufficient data on diffusion limitation and functional impairment. Objective: This study aimed to thoroughly evaluate post-tubercular sequelae after treatment, assessing chest radiology, spirometry, diffusing capacity, and exercise capacity. Methods: A total of 85 patients were studied at a university teaching hospital in Mysuru. The data collected included characteristics, comorbidities, smoking history, and respiratory symptoms. The investigations included spirometry, DLCO, chest X-rays with scoring, and 6MWT. Results: Of the patients, 70% had abnormal X-rays post-treatment, correlating with reduced lung function. Additionally, 70% had impaired spirometry with obstructive/restrictive patterns, and 62.2% had reduced DLCO, with females at higher risk. Smoking increased the risk of sequelae. Conclusions: Most patients had residual radiological/lung function abnormalities post-treatment. Advanced analyses provide insights into obstructive vs. restrictive defects. Ongoing research should explore pathogenetic mechanisms and therapeutic modalities to minimize long-term post-TB disability.

Lung Clearance Index as a Screening Parameter of Pulmonary Impairment in Patients under Immune Checkpoint Therapy: A Pilot Study.

Background: Immune checkpoint blockade (ICB) has presented a breakthrough in the treatment of malignant tumors and increased the overall survival of patients with various tumor entities. ICB may also cause immune-related adverse events, such as pneumonitis or interstitial lung disease. The lung clearance index (LCI) is a multiple-breath washout technique offering information on lung pathology in addition to conventional spirometry. It measures the degree of pulmonary ventilation inhomogeneity and allows early detection of pulmonary damage, especially that to peripheral airways. Methods: This cross-sectional study compared the lung function of patients with melanoma or metastatic cutaneous squamous cell carcinoma who received programmed cell death 1 (PD-1) and cytotoxic T-Lymphocyte-associated Protein 4 (CTLA-4) antibodies, alone or in combination, to age- and sex-matched controls. Lung function was assessed using spirometry, according to American Thoracic Society and European Respiratory Society standards, the LCI, and a diffusion capacity of carbon monoxide (DLCO) measurement. Results: Sixty-one screened patients and thirty-eight screened controls led to nineteen successfully included pairs. The LCI in the ICB-treated patients was 8.41 ± 1.15 (mean ± SD), which was 0.32 higher compared to 8.07 ± 1.17 in the control group, but the difference was not significant (p = 0.452). The patients receiving their ICB therapy for under five months showed a significantly lower LCI (7.98 ± 0.77) compared to the ICB patients undergoing therapy for over five months (9.63 ± 1.22) at the point of testing (p = 0.014). Spirometric analysis revealed that the forced expiratory volume between 25 and 75% of the forced vital capacity (FEF25-75%) in the ICB-treated patients was significantly reduced (p = 0.047) compared to the control group. DLCO (%predicted and adjusted for hemoglobin) was 94.4 ± 19.7 in the ICB patients and 93.4 ± 21.7 in the control group (p = 0.734). Conclusions: The patients undergoing ICB therapy showed slightly impaired lung function compared to the controls. Longer periods of ICB treatment led to deterioration of the LCI, which may be a sign of a subclinical inflammatory process. The LCI is feasible and may be easily integrated into the clinical daily routine and could contribute to early detection of pulmonary (auto-)inflammation.

Whole blood transcriptome in long-COVID patients reveals association with lung function and immune response.

BACKGROUND: Months after infection with severe acute respiratory syndrome coronavirus 2, at least 10% of patients still experience complaints. Long-COVID (coronavirus disease 2019) is a heterogeneous disease, and clustering efforts revealed multiple phenotypes on a clinical level. However, the molecular pathways underlying long-COVID phenotypes are still poorly understood. OBJECTIVES: We sought to cluster patients according to their blood transcriptomes and uncover the pathways underlying their disease. METHODS: Blood was collected from 77 patients with long-COVID from the Precision Medicine for more Oxygen (P4O2) COVID-19 study. Unsupervised hierarchical clustering was performed on the whole blood transcriptome. These clusters were analyzed for differences in clinical features, pulmonary function tests, and gene ontology term enrichment. RESULTS: Clustering revealed 2 distinct clusters on a transcriptome level. Compared with cluster 2 (n = 65), patients in cluster 1 (n = 12) showed a higher rate of preexisting cardiovascular disease (58% vs 22%), higher prevalence of gastrointestinal symptoms (58% vs 29%), shorter hospital duration during severe acute respiratory syndrome coronavirus 2 infection (median, 3 vs 8 days), lower FEV1/forced vital capacity (72% vs 81%), and lower diffusion capacity of the lung for carbon monoxide (68% vs 85% predicted). Gene ontology term enrichment analysis revealed upregulation of genes involved in the antiviral innate immune response in cluster 1, whereas genes involved with the adaptive immune response were upregulated in cluster 2. CONCLUSIONS: This study provides a start in uncovering the pathophysiological mechanisms underlying long-COVID. Further research is required to unravel why the immune response is different in these clusters, and to identify potential therapeutic targets to create an optimized treatment or monitoring strategy for the individual long-COVID patient.

Preoperative DLCO predicts severe early complications after liver transplantation.

BACKGROUND: Severe early complications are common after liver transplantation (LT) and are a key determinant of LT-related morbidity and mortality. The aim of this study was to assess whether lung function measured in the pre-operative period predicted complicated outcomes in the first month after LT. MATERIAL AND METHODS: Patients with mild-to-moderate liver disease (Model for End stage Liver Disease-MELD score≤30) who underwent LT between October 2015 and May 2020 in a single centre were retrospectively included. The primary endpoint was the occurrence of severe early complications after LT defined by mechanical ventilation duration > 2 days or length of ICU stay > 7 days or reintubation or death < 1 month after LT. RESULTS: One hundred and twenty patients were included (age 59 [53-64] years, 72 % men). Forty patients (33 %) had early complications after LT. Measured and%predicted hemoglobin-corrected lung transfer capacity for carbon monoxide (DLCOc) were significantly lower in patients with severe early complications after LT. DLCOc was the only variable that associated independently with severe early complications by multivariate analysis. DLCOc under 16.3 ml.min-1.mmHg-1 predicted respiratory complications with a sensitivity of 67.5 % and a specificity of 62.9 %. DLCOc%pred under 61.5 % had a sensitivity of 56.8 % and a specificity of 72 %. DLCOc independently associated with forced vital capacity (FVC), pulmonary emphysema, and the muscle mass index. CONCLUSION: A decrease in DLCOc indicated an increased risk of severe early complications after LT.

Genetic association between smoking and DLCO in idiopathic pulmonary fibrosis patients.

BACKGROUND: Observational studies have shown that smoking is related to the diffusing capacity of the lungs for carbon monoxide (DLCO) in individuals with idiopathic pulmonary fibrosis (IPF). Nevertheless, further investigation is needed to determine the causal effect between these two variables. Therefore, we conducted a study to investigate the causal relationship between smoking and DLCO in IPF patients using two-sample Mendelian randomization (MR) analysis. METHODS: Large-scale genome-wide association study (GWAS) datasets from individuals of European descent were analysed. These datasets included published lifetime smoking index (LSI) data for 462,690 participants and DLCO data for 975 IPF patients. The inverse-variance weighting (IVW) method was the main method used in our analysis. Sensitivity analyses were performed by MR‒Egger regression, Cochran's Q test, the leave-one-out test and the MR-PRESSO global test. RESULTS: A genetically predicted increase in LSI was associated with a decrease in DLCO in IPF patients [ORIVW = 0.54; 95% CI 0.32-0.93; P = 0.02]. CONCLUSIONS: Our study suggested that smoking is associated with a decrease in DLCO. Patients diagnosed with IPF should adopt an active and healthy lifestyle, especially by quitting smoking, which may be effective at slowing the progression of IPF.

Adipose-derived stromal vascular fraction cells to treat long-term pulmonary sequelae of coronavirus disease 2019: 12-month follow-up.

BACKGROUND AIMS: Long coronavirus disease (COVID) is estimated to occur in up to 20% of patients with coronavirus disease 2019 (COVID-19) infections, with many having persistent pulmonary symptoms. Mesenchymal stromal cells (MSCs) have been shown to have powerful immunomodulatory and anti-fibrotic properties. Autologous adipose-derived (AD) stromal vascular fraction (SVF) contains MSC and other healing cell components and can be obtained by small-volume lipoaspiration and administered on the same day. This study was designed to study the safety of AD SVF infused intravenously to treat the pulmonary symptoms of long COVID. METHODS: Five subjects with persistent cough and dyspnea after hospitalization and subsequent discharge for COVID-19 pneumonia were treated with 40 million intravenous autologous AD SVF cells and followed for 12 months, to include with pulmonary function tests and computed tomography scans of the lung. RESULTS: SVF infusion was safe, with no significant adverse events related to the infusion out to 12 months. Four subjects had improvements in pulmonary symptoms, pulmonary function tests, and computed tomography scans, with some improvement noted as soon as 1 month after SVF treatment. CONCLUSIONS: It is not possible to distinguish between naturally occurring improvement or improvement caused by SVF treatment in this small, uncontrolled study. However, the results support further study of autologous AD SVF as a treatment for long COVID.

One-year follow-up of COVID-19 recoverees with impaired pulmonary function: A prospective cohort study.

Decreased diffusion capacity for carbon monoxide (DLCO) is the most prevalent pulmonary testing abnormality among COVID-19 recoverees. We prospectively followed 51 individuals with impaired DLCO at an average of ∼3 months following COVID-19 and re-examined them at one year. At follow-up, mean DLCO increased from 68.0 % to 72.6 % (p = 0.002); while 33 % of the cohort experienced a clinically significant rise (>10 points) in DLCO, only 29 % normalized their values. While DLCO change did not correlate with symptoms, lack of improvement was more prevalent among individuals with obesity. Regardless of COVID-19 severity, a substantial proportion continued to exhibit DLCO impairment at 1-year.

Pulmonary function testing in preoperative high-risk patients.

BACKGROUND: Postoperative respiratory failure is the most frequent complication in postsurgical patients. The purpose of this study is to assess whether pulmonary function testing in high-risk patients during preoperative assessment detects previously unknown respiratory impairments which may influence patient outcomes. METHODS: A targeted patient screening by spirometry and the measurement of the diffusing capacity of the lung for carbon monoxide (DLCO) was implemented in the anesthesia department of a tertiary university hospital. Patients of all surgical disciplines who were at least 75 years old or exhibited reduced exercise tolerance with the metabolic equivalent of task less than four (MET < 4) were examined. Clinical characteristics, history of lung diseases, and smoking status were also recorded. The statistical analysis entailed t-tests, one-way ANOVA, and multiple linear regression with backward elimination for group comparisons. RESULTS: Among 256 included patients, 230 fulfilled the test quality criteria. Eighty-one (35.2%) patients presented obstructive ventilatory disorders, out of which 65 were previously unknown. 38 of the newly diagnosed obstructive disorders were mild, 18 moderate, and 9 severe. One hundred forty-five DLCO measurements revealed 40 (27.6%) previously unknown gas exchange impairments; 21 were mild, 17 moderate, and 2 severe. The pulmonary function parameters of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and DLCO were significantly lower than the international reference values of a healthy population. Patients with a lower ASA class and no history of smoking exhibited higher FVC, FEV1, and DLCO values. Reduced exercise tolerance with MET < 4 was strongly associated with lower spirometry values. CONCLUSIONS: Our screening program detected a relevant number of patients with previously unknown obstructive ventilatory disorders and impaired pulmonary gas exchange. This newly discovered sickness is associated with low metabolic equivalents and may influence perioperative outcomes. Whether optimized management of patients with previously unknown impaired lung function leads to a better outcome should be evaluated in multicenter studies. TRIAL REGISTRATION: German Registry of Clinical Studies (DRKS00029337), registered on: June 22nd, 2022.

A Comparison of the Effectiveness of Nintedanib and Pirfenidone in Treating Idiopathic Pulmonary Fibrosis: A Systematic Review.

Idiopathic pulmonary fibrosis (IPF), which shares a radiographic pattern with the usual interstitial pneumonia (UIP), is a specific form of chronic and progressive interstitial lung disorder resulting in persistent fibrosis and impaired lung function. Most of the patients suffer from dyspnea which adversely affects health-related quality of life (HRQOL). The underlying etiology of the disease is not yet understood, but research done on the subject reveals that aberrant repair mechanisms and dysregulated immune responses may be the cause. It can affect any age group but predominantly affects patients who are above 50 years of age. It has been observed that in addition to age, the reasons are also related to smoking, pollution, and inhalation of harmful elements. As the cause of IPF is still unknown and there is no cure yet, presently, it is treated to delay lung function loss with antifibrotic medications, nintedanib, and pirfenidone. However, both nintedanib and perfenidone have side effects which affect different patients in different ways and with different levels of severity, thereby making the treatment even more challenging for medical practitioners. The present systematic review aims at studying the efficacy of pirfenidone and nintedanib in relieving symptoms and in extending survival in patients. A detailed search was done in relevant articles listed in PubMed, ScienceDirect, and the New England Journal of Medicine between 2018 and 2023. It was observed that the most accepted way of measuring the progression of IPF is the evaluation of pulmonary function by assessing the forced vital capacity (FVC). Several studies have shown that the decline in FVC over a period of 6-12 months is directly associated with a higher mortality rate. The outcomes were similar in both male and female irrespective of age, gender, and ethnicity. However, some patients being treated with pirfenidone and nintedanib experienced various side-effects which were mainly gastrointestinal like diarrhea, dyspepsia, and vomiting. In the case of pirfenidone, some patients also experienced photosensitivity and skin rashes. In cases where the side-effects are extremely severe and are more threatening than the disease itself, the treatment has to be discontinued. The survival rate in patients with IPF is marked by a median of 3-5 years that is even lower than many cancers; hence, the treatment should be started as soon as the disease is detected. However, further research is needed to establish the etiology of IPF and to establish treatments that can stop its progression.

Preoperative DLco and FEV1 are correlated with postoperative pulmonary complications in patients after esophagectomy.

Limited information is available regarding the association between preoperative lung function and postoperative pulmonary complications (PPCs) in patients with esophageal cancer who undergo esophagectomy. This is a retrospective cohort study. Patients were classified into low and high lung function groups by the cutoff of the lowest fifth quintile of forced expiratory volume in 1 s (FEV1) %predicted (%pred) and diffusing capacity of the carbon monoxide (DLco) %pred. The PPCs compromised of atelectasis requiring bronchoscopic intervention, pneumonia, and acute lung injury/acute respiratory distress syndrome. Modified multivariable-adjusted Poisson regression model using robust error variances and inverse probability treatment weighting (IPTW) were used to assess the relative risk (RR) for the PPCs. A joint effect model considered FEV1%pred and DLco %pred together for the estimation of RR for the PPCs. Of 810 patients with esophageal cancer who underwent esophagectomy, 159 (19.6%) developed PPCs. The adjusted RR for PPCs in the low FEV1 group relative to high FEV1 group was 1.48 (95% confidence interval [CI] = 1.09-2.00) and 1.98 (95% CI = 1.46-2.68) in the low DLco group relative to the high DLco group. A joint effect model showed adjusted RR of PPCs was highest in patients with low DLco and low FEV1 followed by low DLco and high FEV1, high DLco and low FEV1, and high DLco and high FEV1 (Reference). Results were consistent with the IPTW. Reduced preoperative lung function (FEV1 and DLco) is associated with post-esophagectomy PPCs. The risk was further strengthened when both values decreased together.

Clinical Correlates of a Nonplexiform Vasculopathy in Patients With a Diagnosis of Idiopathic Pulmonary Arterial Hypertension.

BACKGROUND: The clinical phenotype of patients with idiopathic pulmonary arterial hypertension (IPAH) has changed. Whether subgroups of patients with IPAH have different vascular phenotypes is a subject of debate. RESEARCH QUESTION: What are the histologic patterns and their clinical correlates in patients with a diagnosis of IPAH or hereditary pulmonary arterial hypertension? STUDY DESIGN AND METHODS: In this this cross-sectional registry study, lung histology of 50 patients with IPAH was assessed qualitatively by two experienced pathologists. In addition, quantitative analysis by means of histopathologic morphometry using immunohistochemistry was performed. Histopathologic characteristics were correlated with clinical and hemodynamic parameters. RESULTS: In this cohort of 50 patients with IPAH, a plexiform vasculopathy was observed in 26 of 50 patients (52%), whereas 24 of 50 patients (48%) showed a nonplexiform vasculopathy. The nonplexiform vasculopathy was characterized by prominent pulmonary microvascular (arterioles and venules) remodeling and vascular rarefaction. Although hemodynamic parameters were comparable in plexiform vs nonplexiform vasculopathy, patients with nonplexiform vasculopathy were older, more often were male, more often had a history of cigarette smoking, and had lower diffusing capacity of the lungs for carbon monoxide at diagnosis. No mutations in established pulmonary arterial hypertension genes were found in the nonplexiform group. INTERPRETATION: This study revealed different vascular phenotypes within the current spectrum of patients with a diagnosis of IPAH, separated by clinical characteristics (age, sex, history of cigarette smoking, and diffusing capacity of the lungs for carbon monoxide at diagnosis). Potential differences in underlying pathobiological mechanisms between patients with plexiform and nonplexiform microvascular disease should be taken into account in future research strategies unravelling the pathophysiologic features of pulmonary hypertension and developing biology-targeted treatment approaches.

Influence of Impaired Diffusing Capacity and Sleep-disordered Breathing on Nocturnal Hypoxemia and Health Outcomes in Men with and without Human Immunodeficiency Virus.

Rationale: Nocturnal hypoxemia is common in sleep-disordered breathing (SDB) and is associated with increased morbidity and mortality. Although impaired diffusing capacity of the lung for carbon monoxide (DlCO) is associated with daytime hypoxemia, its influence on SDB-related nocturnal hypoxemia is not known. Objectives: To characterize the effects of DlCO impairment on SDB-related nocturnal hypoxemia and associated health outcomes. Methods: Data from a multicenter cohort of men with and without human immunodeficiency virus (HIV) infection, with concomitant measures of DlCO and home-based polysomnography (n = 544), were analyzed. Multivariable quantile regression models characterized associations between DlCO and several measures of SDB-related hypoxemia (e.g., total sleep time with oxygen saturation as measured by pulse oximetry [SpO2] < 90% [T90]). Structural equation models were used to assess associations of impaired DlCO and SDB-related hypoxemia measures with prevalent hypertension and type 2 diabetes. Results: DlCO impairment (<80% predicted) was associated with sleep-related hypoxemia. Participants with severe SDB (apnea-hypopnea index ⩾ 30 events/h) and impaired DlCO had higher T90 (median difference, 15.0% [95% confidence interval (CI), 10.3% to 19.7%]) and average SDB-related desaturation (median difference, 1.0 [95% CI, 0.5 to 1.5]) and lower nadir SpO2 (median difference, -8.2% [95% CI, -11.4% to -4.9%]) and average SpO2 during sleep (median difference, -1.1% [95% CI, -2.1% to -0.01%]) than those with severe SDB and preserved DlCO. Higher T90 was associated with higher adjusted odds of prevalent hypertension (odds ratio, 1.39 [95% CI, 1.14 to 1.70]) and type 2 diabetes (odds ratio, 1.25 [95% CI, 1.07 to 1.46]). Conclusions: DlCO impairment in severe SDB was associated with sleep-related hypoxemia, prevalent hypertension, and type 2 diabetes. Assessment of SDB should be considered in those with impaired DlCO to guide testing and risk stratification strategies.

Adjusting diffusing capacity for anemia in patients undergoing allogeneic HCT: a comparison of two methodologies.

BACKGROUND: Diffusing capacity (DLCO) measurements are affected by hemoglobin. Two adjustment equations are used: Cotes (recommended by ATS/ERS) and Dinakara (used in the hematopoietic stem cell transplantation comorbidity index [HCT-CI]). It is unknown how these methods compare, and which is better from a prognostication standpoint. STUDY DESIGN: This is a retrospective cohort of 1273 adult patients who underwent allogeneic HCT, completed a pre-transplant DLCO and had a concurrent hemoglobin measurement. Non-relapse mortality was measured using competing risk analysis. RESULTS: Patients had normal spirometry (FEV1 99.7% [IQR: 89.4-109.8%; FVC 100.1% [IQR: 91.0-109.6%] predicted), left ventricular ejection fraction (57.2[6.7]%) and right ventricular systolic pressure (30.1[7.0] mmHg). Cotes-DLCO was 85.6% (IQR: 76.5-95.7%) and Dinakara-DLCO was 103.6% (IQR: 90.7-117.2%) predicted. For anemic patients (Hb<10g/dL), Cotes-DLCO was 84.2% (IQR: 73.9-94.1%) while Dinakara-DLCO 111.0% (97.3-124.7%) predicted. Cotes-DLCO increased HCT-CI score for 323 (25.4%) and decreased for 4 (0.3%) patients. Cotes-DLCO was superior for predicting non-relapse mortality: for both mild (66-80% predicted, HR 1.55 [95%CI: 1.26-1.92, p < 0.001]) and moderate (<65% predicted, HR 2.11 [95%CI: 1.55-2.87, p<0.001]) impairment. In contrast, for Dinakara-DLCO, only mild impairment (HR 1.69 [95%CI 1.26-2.27, p < 0.001]) was associated with lower survival while moderate impairment was not (HR 1.44 [95%CI: 0.64-3.21, p = 0.4]). In multivariable analyses, after adjusting for demographics, hematologic variables, cardiac function and FEV1, Cotes-DLCO was predictive of overall survival at 1-year (OR 0.98 [95%CI: 0.97-1.00], p = 0.01), but Dinakara-DLCO was not (OR 1.00 [95%CI: 0.98-1.00], p = 0.20). CONCLUSION: The ERS/ATS recommended Cotes method likely underestimates DLCO in patients with anemia, whereas the Dinakara (used in the HCT-CI score) overestimates DLCO. The Cotes method is superior to the Dinakara method score in predicting overall survival and relapse-free survival in patients undergoing allogeneic HCT.

Chronic Obstructive Pulmonary Disease and Non-Small Cell Lung Cancer an association.

Objectives: Lung cancer is known to be associated with chronic obstructive pulmonary disease. Moreover; nutritional status is associated with chronic obstructive disease treatment and lung cancer. Our aim was to evaluate the interaction of the COPD status and treatment of non-small cell lung cancer. Methods: Eighty-two patients were enrolled in our multicenter study. Chronic obstructive disease stage, spirometry and treatment was recorded along with the treatment and Body Mass Index (BMI), Mediterranian Diet Score, Pack Years, Basic Metabolsim (RMR) (kcal/day), VO2 (ml/min), Ve (lt/min) and Physical Activity. The statistical analysis was performed using the JMP 14.3 (SAS Inc 2018) software. Results: The drug pairs showed a steady and unchanged by time health condition for 48 patients. Overall, 31 patients were recorded with worse COPD health conditions. The one-way ANOVA clearly indicated that chemotherapy induced the best FEV1-difference conditions with a positive effect of 8.56 mean FEV volume, the combined treatment simply did not have an effect (-0.9), while immunotherapy and patients receiving radiation decreased their FEV1 volume down to -4.23 and -5.15 mean values. Conclusions: Patients receiving chemotherapy alone had their chronic obstructive disease improved with less drugs and exacerbations, while patients receiving immunotherapy had their chronic obstructive disease stable, while all other treatment combinations worsened the patients chronic obstructive disease. Nutritional status did not affect the chronic obstructive disease of these patients in any way.