Pulmonary Impairment Research Articles

Sleep-Disordered Breathing, Hypoxia, and Pulmonary Physiologic Influences in Atrial Fibrillation.

Background We leverage a large clinical cohort to elucidate sleep-disordered breathing and sleep-related hypoxia in incident atrial fibrillation (AF) development given the yet unclear contributions of sleep-related hypoxia and pulmonary physiology in sleep-disordered breathing and AF. Methods and Results Patients who underwent sleep studies at Cleveland Clinic January 2, 2000, to December 30, 2015, comprised this retrospective cohort. Cox proportional hazards models were used to examine apnea hypopnea index, percentage time oxygen saturation <90%, minimum and mean oxygen saturation, and maximum end-tidal carbon dioxide on incident AF adjusted for age, sex, race, body mass index, cardiopulmonary disease and risk factors, antiarrhythmic medications, and positive airway pressure. Those with spirometry were additionally adjusted for forced expiratory volume in 1 second, forced vital capacity, and forced expiratory volume in 1 second/forced vital capacity. This cohort (n=42 057) was 50.7±14.1 years, 51.3% men, 74.1% White individuals, had median body mass index 33.2 kg/m2, and 1947 (4.6%) developed AF over 5 years. A 10-unit apnea hypopnea index increase was associated with 2% higher AF risk (hazard ratio [HR], 1.02 [95% CI, 1.00-1.03]). A 10-unit increase in percentage time oxygen saturation <90% and 10-unit decreases in mean and minimum oxygen saturation were associated with 6% (HR, 1.06 [95% CI, 1.04-1.08]), 30% (HR, 1.30 [95% CI, 1.18-1.42]), and 9% (HR, 1.09 [95% CI, 1.03-1.15]) higher AF risk, respectively. After adjustment for spirometry (n=9683 with available data), only hypoxia remained significantly associated with incident AF, although all coefficients were stable. Conclusions Sleep-related hypoxia was associated with incident AF in this clinical cohort, consistent across 3 measures of hypoxia, persistent after adjustment for pulmonary physiologic impairment. Findings identify a strong role for sleep-related hypoxia in AF development without pulmonary physiologic interdependence.

Anesthesia For Patients Receiving Single-Lung Transplantation in Non-Pulmonary Surgical Intervention: A Case Report

With improvements in the survival rate following lung transplantation, lung transplant recipients occasionallyundergo subsequent non-pulmonary surgical interventions that are not directly related to their pulmonary disease. Bothanesthesia and surgical procedures can affect the transplanted lungs and other organs in such patients. Moreover, these patients may show pulmonary function impairment; depending on the type of surgery and anatomical site. An adequate understanding of the physiology of the transplanted lung, careful preoperative evaluation and preparation, appropriate utilization of airway equipment, and proper management of intraoperative fluids and ventilation are crucial for superior perioperative outcomes.

Real-World Outcomes of Brexucabtagene Autoleucel (Brexu-cel) for Relapsed or Refractory (R/R) Mantle Cell Lymphoma (MCL): A CIBMTR Subgroup Analysis of High-Risk Characteristics

Background: Patients (pts) with R/R MCL and TP53 mutation/deletion, or high Ki-67 proliferation index (PI), have historically had limited treatment options with dismal outcomes. Brexu-cel is a CAR T-cell therapy approved in the US for adults with R/R MCL. Real-world data has been consistent with that of clinical trials (Kambhampati et al. 2023). In a 3-year follow-up of ZUMA-2 (Wang et al. 2022), outcomes were comparable across various high-risk subgroups (TP53 mutation, Ki-67 PI ≥ 30% or ≥ 50%). Here, we describe real-world outcomes of brexu-cel in R/R MCL by high-risk features, including deletion of TP53 or 17p, Ki-67 PI, and by ZUMA-2 eligibility. Methods : A total of 500 pts receiving brexu-cel for R/R MCL from 84 US centers between 07/2020−12/2022 were prospectively enrolled in the CIBMTR observational database for a post-authorization safety study. In this analysis, 446 pts were included, excluding pts with prior non-transplant cellular therapy, missing data for analysis, or no follow-up. Effectiveness outcomes were overall response rate (ORR), complete response (CR) rate, duration of response (DOR), progression-free survival (PFS), overall survival (OS) and relapse/progressive disease (REL/PD). Safety outcomes included cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), prolonged cytopenias, infections requiring treatment, subsequent neoplasms, and non-relapse mortality (NRM). Analyses conducted included univariate as well as multivariate logistic regression and Cox proportional hazard models fit to identify covariates with an impact on outcomes. Results : Of the 446 pts included and who had available data, 20% (44/220) had deletion of TP53/17p at diagnosis; Ki-67 PI ≥ 50% at diagnosis was seen in 42% (107/252). Pts with deletion of TP53/17p were less likely to undergo prior autologous hematopoietic cell transplant (11% vs 30%). Pts with Ki-67 PI ≥ 50% were more likely to receive Bruton's tyrosine kinase inhibitor (BTKi) (92% vs 81%) and bridging therapy (52% vs 37%), but less likely to receive bendamustine (47% vs 62%). Pts with either high-risk feature tended to have a shorter time from diagnosis to brexu-cel infusion. Overall, 67% (297/446) of pts would not have met ZUMA-2 eligibility criteria, mainly due to pulmonary impairment (33%), cardiac impairment (21%), prior malignancy (21%), low platelet count (20%), and no prior BTKi (18%). With a median follow-up of 12.2 mo, DOR, PFS and OS were evaluated at 12 mo. CR was 84% (ORR, 95%; DOR, 46%; PFS, 54%; OS, 55%) for pts with deletion of TP53/17p vs 80% (ORR, 90%; DOR, 65%; PFS, 61%; OS, 77%) in those without. CR for pts with Ki-67 PI ≥ 50% vs &amp;lt; 50% was 84% (ORR, 93%; DOR, 60%; PFS, 58%; OS, 77%) vs 83% (ORR, 92%; DOR, 69%; PFS, 63%; OS, 73%); for pts eligible vs ineligible to ZUMA-2, CR was 84% (ORR, 92%; DOR, 73%; PFS, 70%; OS, 82%) vs 79% (ORR, 90%; DOR, 60%; PFS, 57%; OS, 71%). Safety endpoints were largely consistent among all subgroups. Prolonged neutropenia and thrombocytopenia occurred more frequently in pts with vs without deletion of TP53/17p (25% vs 12% and 28% vs 17%, respectively). Grade ≥ 3 CRS occurred more frequently in ZUMA-2-ineligible vs eligible pts (13% vs 7%). After multivariable adjustment, all effectiveness and most safety outcomes were consistent regardless of deletion of TP53/17p. Deletion of TP53/17p approached an association with decreased OS (HR 1.79 [95% CI 0.99−3.25]), and was associated with more frequent prolonged neutropenia (OR 2.85 [1.30−6.27]) and prolonged thrombocytopenia (OR 2.18 [1.04−4.57]) although these did not result in significant difference in infections requiring treatment (HR 1.22 [0.79−1.90]) nor NRM (HR 2.00 [0.77−5.21]). The remaining outcomes were consistent regardless of deletion of TP53/17p. Comparable outcomes were observed between pts with Ki-67 PI ≥ 50% and &amp;lt; 50%. Conclusions: These real-world findings with 12 mo of follow-up suggest that outcomes of brexu-cel treatment are largely consistent, including a high CR rate, regardless of ZUMA-2 eligibility or the high-risk feature subgroups analyzed. Although pts without deletion of TP53/17p appeared to have longer OS than pts with deletion of TP53/17p, the data further support brexu-cel as the standard of care across pts with R/R MCL, including those with high-risk features. An updated dataset is planned to be analyzed and results can be presented at the conference. *SK and NA are equal contributors.

Impacts of covid-19 on sleep quality and autonomic function in elderly diabetic women.

to analyze the quality of sleep and cardiac autonomic modulation of elderly diabetic women in the post-covid-19 syndrome. 41 elderly women, aged 60-75years, with a diagnosis of Type 2 Diabetes Mellitus and who had covid-19 were included, divided into three groups: 14 in the Diabetes without covid-19 group (DG), 15 in the Diabetes with covid-19 group (CG), 12 in the Diabetes with covid-19 group who had Pulmonary Compromise (IG). Sleep quality was assessed using the Pittsburgh questionnaire, anamnesis, capillary blood glucose, blood pressure collection, anthropometry, resting electrocardiogram for 10min for heart rate variability (HRV) analysis. Data were analyzed by 1-way ANOVA followed by Tukey-Kramer Multiple Comparisons Test, significance for p≤0.05. there was no significant difference in age, blood glucose, blood pressure, and body composition between the groups. In the analysis of sleep quality, there was significance in the following indices: sleep duration, sleep efficiency, sleep disturbances, and daytime sleepiness. Further, there was a reduction in autonomic indices between CG vs. DG: VarRR (ms2), SDNN (ms), SD1 (ms), TINN (ms), HF-log (ms2), LF-log (ms2); and between IG vs. DG: VarRR (ms2), SDNN (ms), RMSSD (ms), SD1 (ms), SD2 (ms), and HF-log (ms2). it is suggestive that diabetic elderly women who had covid-19, with and without pulmonary impairment, have impaired sleep quality and interference on HRV with decreased parasympathetic autonomic modulation.

Alveolar Hyperoxia and Exacerbation of Lung Injury in Critically Ill SARS-CoV-2 Pneumonia.

Acute hypoxic respiratory failure (AHRF) is a prominent feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) critical illness. The severity of gas exchange impairment correlates with worse prognosis, and AHRF requiring mechanical ventilation is associated with substantial mortality. Persistent impaired gas exchange leading to hypoxemia often warrants the prolonged administration of a high fraction of inspired oxygen (FiO2). In SARS-CoV-2 AHRF, systemic vasculopathy with lung microthrombosis and microangiopathy further exacerbates poor gas exchange due to alveolar inflammation and oedema. Capillary congestion with microthrombosis is a common autopsy finding in the lungs of patients who die with coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome. The need for a high FiO2 to normalise arterial hypoxemia and tissue hypoxia can result in alveolar hyperoxia. This in turn can lead to local alveolar oxidative stress with associated inflammation, alveolar epithelial cell apoptosis, surfactant dysfunction, pulmonary vascular abnormalities, resorption atelectasis, and impairment of innate immunity predisposing to secondary bacterial infections. While oxygen is a life-saving treatment, alveolar hyperoxia may exacerbate pre-existing lung injury. In this review, we provide a summary of oxygen toxicity mechanisms, evaluating the consequences of alveolar hyperoxia in COVID-19 and propose established and potential exploratory treatment pathways to minimise alveolar hyperoxia.

Influence of kyphosis in ankylosing spondylitis on cardiopulmonary functions.

This paper aims at analyzing the characteristics of cardiopulmonary functions in the patients with ankylosing spondylitis (AS), and exploring the influence of global kyphosis (GK) on cardiopulmonary functions. Clinical data of 46 patients with AS and kyphosis, who had been admitted in our hospital from October 2021 to October 2022, were analyzed retrospectively. According to the to global kyphosis (GK) angle, 23 subjects were divided into Severe Group (GK > 95°), and 23 subjects were divided into in the Moderate Group (80° ≤ GK ≤ 95°). Cardiac structure and cardiopulmonary function parameters were compared between both groups, and the influences of GK Angle on other parameters were analyzed by Pearson or Spearman correlation analysis. The cardiac structure and function measurements in both groups were within the normal range. The pulmonary functions of both groups decreased to different extents. Correlation analysis showed that GK Angle was significantly negatively correlated with the left atrioventricular size (LAD, LVDD, LVSD) and diastolic function parameters (E/A, e'/a') in the patients with AS (P < .05); GK Angle was negatively correlated with restrictive ventilation parameters in the patients with AS (P < .05). The GK Angle of the patients with AS affects the cardiac structure and diastolic function. The larger the GK Angle is, the smaller the left and right at ventricle diameters are. In addition, GK Angle also affects the left ventricular diastolic function. GK Angle is related to the degree of pulmonary function impairment, and the larger the GK Angle is, the worse the pulmonary function it will be.

High-Resolution CT Scan Fibrotic Patterns in Stage IV Pulmonary Sarcoidosis: Impact on Pulmonary Function and Survival

Different patterns of fibrosis on high-resolution CT scans (HRCT) have been associated with reduced survival in some interstitial lung diseases. Nothing is known about HRCT scan patterns and survival in sarcoidosis. Will a detailed description of the extent and pattern of HRCT scan fibrosis in patients with stage IV pulmonary sarcoidosis impact pulmonary function and survival? Two hundred forty patients with stage IV sarcoidosis at two large tertiary institutions were studied. The earliest HRCT scan with fibrosis was reviewed for extent of fibrosis (< 10%, 10%-20%, and > 20%) and presence of bronchiectasis, upper lobe fibrocystic changes, basal subpleural honeycombing, ground-glass opacities (GGOs), large bullae, and mycetomas. Presence of sarcoidosis-associated pulmonary hypertension (SAPH) and pulmonary function testing performed within 1 year of HRCT were recorded. Patients were followed up until last clinic visit, death, or lung transplantation. The mean age was 58.4 years. Seventy-four percent were Black, 63%were female, and mean follow-up was 7.4 years. Death or LT occurred in 53 patients (22%). Thirty-one percent had > 20%fibrosis, 25%had 10%-20%fibrosis, and 44%had< 10%fibrosis. The most common HRCT abnormalities were bronchiectasis (76%), upper lobe fibrocystic changes (36%), and GGOs (28%). Twelve percent had basal subpleural honeycombing, and 32%had SAPH. Patients with > 20%fibrosis had more severe pulmonary impairment, were more likely to have SAPH (53%), and had worse survival (44%mortality; P< .001). Upper lobe fibrocystic changes, basal subpleural honeycombing, and large bullae were associated with worse pulmonary function and worse survival. Patients with basal subpleural honeycombing had the worst pulmonary function and survival (55%mortality; P< .001). GGOs were associated with worse pulmonary function but not worse survival, and mycetomas were associated with worse survival but not worse pulmonary function. A Cox proportional hazards model indicated that basal subpleural honeycombing (hazard ratio, 7.95), diffusion capacity for carbon monoxide< 40%(HR, 5.67) and White race (hazard ratio, 2.61) were independent predictors of reduced survival. HRCT scan features of fibrotic pulmonary sarcoidosis had an impact on pulmonary function and survival. Presence of >20%fibrosis and basal subpleural honeycombing are predictive of worse pulmonary function and worse survival in patients with stage IV pulmonary sarcoidosis.

Identification of clinical factors impacting outcome in patients undergoing autologous hematopoietic cell transplantation after BEAM and TEAM conditioning.

Organ dysfunction, including pulmonary function impairment, plays a key role in the choice of conditioning chemotherapy before autologous hematopoietic stem cell transplantation (auto-HSCT). Replacement of BCNU/carmustine as part of BEAM (BCNU/carmustine, etoposide, cytarabine, and melphalan) conditioning protocol by thiotepa (TEAM) reduces pulmonary toxicity while maintaining efficacy. We retrospectively analyzed the association of clinical characteristics, comorbidities, and organ function with outcomes after conditioning with BEAM or TEAM. Three hundred ninety-six patients undergoing auto-HSCT (n = 333 with BEAM; n = 63 with TEAM) at our institution between 2008 and 2021 were included in this study. In the multivariate analysis, CO-diffusion capacity corrected for hemoglobin (DLCOcSB) ≤ 60% of predicted, progressive disease (PD) before auto-HSCT, Karnofsky performance score (KPS) ≤ 80%, HCT-CI score ≥ 4, and cardiac disease before auto-HSCT were associated with decreased overall survival (OS) in patients treated with BEAM. In contrast, only PD before auto-HSCT was identified in patients treated with TEAM. Patients conditioned with BEAM and DLCOcSB ≤ 60% had higher non-relapse mortality, including pulmonary cause of death. In summary, we have identified clinical and pulmonary risk factors associated with worse outcomes in patients conditioned with BEAM compared to TEAM. Our data suggest TEAM conditioning as a valid alternative for patients with comorbidities, including pulmonary dysfunction and/or poorer performance scores, before auto-HSCT.

Survival Impacts of Impaired Lung Functions and Comorbidities on Elderly Esophageal Cancer Patients.

Preoperative physiological assessments are crucial for optimizing clinical outcomes, especially those of elderly esophageal cancer (EC) patients who are generally frail and at the high risk of mortality. Patients who underwent surgery for EC between 2004 and 2018 were retrospectively reviewed. Patients were categorized into elderly (>70years) or non-elderly (≤70years) groups. Various physiological parameters including the Charlson Comorbidity Index (CCI), immunonutritional parameters and pulmonary functions were studied. Pulmonary functions included %vital capacity (VC) and forced expiratory volume in one second (FEV1.0) and FEV1.0%. The thresholds were set as the lowest quartile (100% for %VC and 2L for FEV1.0) in this cohort. Multivariate Cox hazards models were applied to determine independent predictors of non-EC-related deaths. In total, 824 patients were included (elderly; n = 306, non-elderly; n = 518). Elderly patients had a significantly lower 5-year OS rate than non-elderly patients (53.3% vs. 57.2%, P = 0.03), mainly due to increased risk of death from non-EC related causes. In the elderly group, multivariate Cox hazards analysis identified 3 independent predictors of non-EC-related deaths; high CCI (HR 1.98, P=0.006), low %VC (HR 2.01, P = 0.004) and low FEV1.0 (HR 1.6, P=0.048). Elderly patients without risk factors had a significantly better 5-year OS rate (63.5%) than those with 1 (50.0%) or 2-3 (36.3%) risk factors (P <0.01). Deaths due to pulmonary disease rose significantly as the number of risk factors increased (P=0.03). The severity of comorbidities and pulmonary function impairments are useful for predicting long-term outcomes, especially non-EC-related deaths, in elderly EC patients.

Risk of subsequent lower respiratory tract infection (LRTI) after hospitalization for COVID-19 LRTI and non-COVID-19 LRTI: a retrospective cohort study

BackgroundRespiratory pathogens, including SARS-CoV-2, can cause pulmonary structural damage and physiologic impairment, which may increase the risk of subsequent lower respiratory tract infections (LRTI). Prior hospitalization for any reason is a risk factor for LRTI, but data on the risk of subsequent new-onset LRTI following hospitalization for COVID-19 LRTI or non-COVID-19 LRTI are needed to inform strategies for immunizations targeting respiratory pathogens.MethodsWe conducted a retrospective cohort study at Kaiser Permanente Southern California (KPSC) among adults hospitalized from 3/1/2020 to 5/31/2022, excluding labor and delivery. We categorized individuals into 3 mutually exclusive baseline exposure groups: those hospitalized for COVID-19 LRTI, those hospitalized for non-COVID-19 LRTI, and those hospitalized for all other causes without LRTI or COVID-19 (“non-LRTI”). Following hospital discharge, patients were followed up for new-onset LRTI, beginning 30 antibiotic-free days after hospital discharge until 8/31/2022. We used multivariable cause-specific Cox regression with time-varying covariates to estimate hazard ratios (HR) of new-onset LRTI comparing those hospitalized for COVID-19 LRTI or non-COVID-19 LRTI to those hospitalized for non-LRTI, adjusting for demographic and clinical characteristics.ResultsThe study included 22,417 individuals hospitalized for COVID-19 LRTI, 12,795 individuals hospitalized for non-COVID-19 LRTI, and 176,788 individuals hospitalized for non-LRTI. Individuals hospitalized for non-COVID-19 LRTI were older and had more comorbidities than those hospitalized for COVID-19 LRTI or non-LRTI. Incidence rates per 1,000 person-years (95% CI) of new-onset LRTI were 52.5 (51.4–53.6) among individuals hospitalized for COVID-19 LRTI, 253.5 (243.7–263.6) among those hospitalized for non-COVID-19 LRTI, and 52.5 (51.4–53.6) among those hospitalized for non-LRTI. The adjusted hazard of new-onset LRTI during follow-up was 20% higher among individuals hospitalized for COVID-19 LRTI (HR 1.20 [95% CI: 1.12–1.28]) and 301% higher among individuals hospitalized for non-COVID-19 LRTI (HR 3.01 [95% CI: 2.87–3.15]) compared to those hospitalized for non-LRTI.ConclusionThe risk of new-onset LRTI following hospital discharge was high, particularly among those hospitalized for non-COVID-19 LRTI, but also for COVID-19 LRTI. These data suggest that immunizations targeting respiratory pathogens, including COVID-19, should be considered for adults hospitalized for LRTI prior to hospital discharge.

Clinical Characteristics and Prognostic Value of Ro52/SSA Antibodies in Idiopathic Inflammatory Myopathies.

Anti-Ro52 are myositis-associated antibodies found in idiopathic inflammatory myopathies (IIMs). This chart review aims to evaluate the frequency, significance, and associated clinical characteristics of Ro52/SSA positivity in IIM patients. We performed a chart review of IIM patients diagnosed between January 2006 and December 2020. All patients met either the 1975 Bohan and Peter or the European League Against Rheumatism/American College of Rheumatology classification criteria for probable or definite myositis. Demographics, clinical and serologic parameters, treatments, and outcomes were compared in patients with anti-Ro52/SSA antibodies and patients without anti-Ro52/SSA antibodies. One hundred eighty-nine patients with IIM were tested for either Ro52 or SSA, with 45 positive for Ro52/SSA (23.8%). Patients with IIM and Ro52/SSA+ were younger at age at onset of disease (44.8 vs. 51.2 years, p = 0.008). Ro52/SSA+ was more common in antisynthetase syndrome (p < 0.001; odds ratio [OR], 4.44; 95% confidence interval [CI], 2.11-9.33) and not frequently identified in clinically amyopathic dermatomyositis (CADM) (p = 0.02; OR, 0.13; 95% CI, 0.02-0.96) or immune-mediated necrotizing myopathy (p = 0.003; OR, 0.14; 95% CI, 0.03-0.63). Of the extraskeletal muscle manifestations, interstitial lung disease (ILD) was strongly associated with Ro52/SSA+ (p < 0.001; OR, 6.61; 95% CI, 3.15-13.86), as was dysphagia (p = 0.006; OR, 2.73; 95% CI, 1.31-5.71). Interstitial lung disease pattern and pulmonary function testing impairment did not differ based on antibody status. There was no significant difference in outcomes between groups. In this myositis cohort, Ro52/SSA+ was present in nearly one-fourth of the population and had a strong association with the antisynthetase syndrome subtype, ILD, and dysphagia. Although these disease manifestations are associated with significant morbidity, in our cohort, they were not associated with increased mortality or more severe ILD.

Pulmonary sarcoidosis: A comprehensive review: Past to present

Sarcoidosis is a sterile non-necrotizing granulomatous disease without known causes that can involve multiple organs with a predilection for the lung and thoracic lymph nodes. Worldwide it is estimated to affect 2–160/100,000 people and has a mortality rate over 5 years of approximately 7%. For sarcoidosis patients, the cause of death is due to sarcoid in 60% of the cases, of which up to 80% are from advanced cardiopulmonary failure (pulmonary hypertension and respiratory microbial infections) in all races except in Japan were greater than 70% of the sarcoidosis deaths are due to cardiac sarcoidosis.Scadding stages for pulmonary sarcoidosis associates with clinical outcomes. Stages I and II have radiographic remission in approximately 30%–80% of cases. Stage III only has a 10%–40% chance of resolution, while stage IV has no change of resolution. Up to 40% of pulmonary sarcoidosis patients progress to stage IV disease with lung parenchyma fibroplasia, bronchiectasis with hilar retraction and fibrocystic disease. These patients are at highest risk for the development of precapillary pulmonary hypertension, which may occur in up to 70% of these patients. Sarcoid patients with pre-capillary pulmonary hypertension can respond to targeted pulmonary arterial hypertension medications. Stage IV fibrocytic sarcoidosis with significant pulmonary physiologic impairment, >20% fibrosis on HRCT or pre-capillary pulmonary hypertension have the highest risk of mortality, which can be >40% at 5-years.First line treatment for patients who are symptomatic (cough and dyspnea) with parenchymal infiltrates and abnormal pulmonary function testing (PFT) is oral glucocorticoids, such as prednisone with a typical starting dose of 20–40 mg daily for 2 weeks to 2 months. Prednisone can be tapered over 6–18 months if symptoms, spirometry, PFTs, and radiographs improve. Prolonged prednisone may be required to stabilize disease. Patients requiring prolonged prednisone ≥10 mg/day or those with adverse effects due to glucocorticoids may be prescribed second and third line treatements. Second and third line treatments include immunosuppressive agents (e.g., methotrexate and azathioprine) and anti-tumor necrosis factor (TNF) medication; respectively. Effective treatments for advanced fibrocystic pulmonary disease are being explored. Despite different treatments, relapse rates range from 13% to 75% depending on the stage of sarcoid, number of organs involved, socioeconomic status, and geography. ConclusionThe mortality rate for sarcoidosis over a 5 year follow up is approximately 7%. Unfortunately, 10%–40% of patients with sarcoidosis develop progressive pulmonary disease, and >60% of deaths resulting from sarcoidosis are due to advance cardiopulmonary disease. Oral glucocorticoids are the first line treatment, while methotrexate and azathioprine are considered second and anti-TNF agents are third line treatments that are used solely or as glucocorticoid sparing agents for symptomatic extrapulmonary or pulmonary sarcoidosis with infiltrates on chest radiographs and abnormal PFT. Relapse rates have ranged from 13% to 75% depending on the population studied.

Risk factors and biomarkers for post-tuberculosis lung damage in a Chinese cohort of male smokers and non-smokers: protocol for a prospective observational study

IntroductionPost-tuberculosis lung damage (PTLD) refers to the residual pulmonary impairment following the completion of antituberculosis (TB) therapy, characterised by persistent respiratory symptoms and abnormal pulmonary function. The risk factors and...

The Effect of Inspiratory Muscle Training in Patients With Lung Cancer After Surgery: A Systematic Review

Objective: The standard of care treatment of potentially resectable lung cancer (LC) is surgery. However, postoperative pulmonary complications (PPCs) and impairments in physical capacity are common. Recently, the effect of inspiratory muscle training (IMT) in postoperative patients with LC (PWLC) was investigated in these outcomes in different studies. The purpose of this systematic review was to synthesize the effect of postoperative IMT (P-IMT) on PPCs and physical capacity in PWLC. Database: PubMed, EMBASE, Cochrane, and CINAHL were searched. Study Selection: Randomized controlled trials, including control/sham group, IMT as the intervention group, and key measures including PPCs, 6-minute walk test (6MWT), Vo 2peak, maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), quality of life (QoL), physical activity level, hospital length of stay, spirometry. Data Synthesis: The quality of the studies was assessed using the Physiotherapy Evidence Database (PEDro) scale. The outcome findings were compared and interpreted. Results: Five studies with 249 patients were analyzed. The PEDro scores of studies ranged from 6 to 8. There is no significant difference in PPCs between the groups. The effects of P-IMT on the 6MWT, Vo 2Peak, MIP, MEP, and QoL were ambiguous. No effect of P-IMT on spirometry was reported. Conclusion: No effect of P-IMT in PPCs was reported. The effect of P-IMT on physical capacity and respiratory muscle strength was not observed. The level of the effect of P-IMT on hospital length of stay and postoperative physical activity was low. No optimal setting of P-IMT for PWLC with surgery was found. More studies are needed.

Outpatient management of sarcoidosis in the COVID-19 pandemic

Introduction. COVID-19 infection alters the body’s immune tolerance, which can affect the course of systemic diseases caused by alterations in immune function. Patients with sarcoidosis, just like patients with systemic diseases, have impaired immune system function. They receive immunosuppressive therapy, so they are at risk of infectious diseases, including the viral ones.Aim. To investigate the course of sarcoidosis in the period 2020-2022, the incidence of COVID-19 infection in patients treated by the pulmonologist of the sarcoidosis-polyclinic office of the Krasnoyarsk Regional Clinical Hospital and to evaluate the incidence of sarcoidosis after COVID-19.Materials and methods. 301 outpatient charts of patients diagnosed with sarcoidosis were analyzed. Anamnestic data, information on vaccination against COVID-19, results of physical examination, multispiral computed tomography of thoracic organs in dynamics, data and methods of morphological verification, the volume of the received therapy for sarcoidosis were assessed.Results. There was evidence that the combination of active sarcoidosis and COVID-19 did not contribute to a severe course of viral infection and progression in the course of granulomatosis. In patients with baseline moderate or severe pulmonary function impairment due to sarcoidosis and long-term use of systemic glucocorticosteroids, no increase in the incidence of adverse COVID-19 outcomes was noted. When analyzing fatal cases, it became known that in the first case, chronic recurrent sarcoidosis and prolonged use of systemic glucocorticosteroids were the factors determining the adverse prognosis in COVID- 19 In the second case, the combination of sarcoidosis with cardiovascular disease, diabetes mellitus, and obesity were adverse outcome factors. New cases of sarcoidosis after COVID-19 have been reported, this may be explained by the interaction between SARS-CoV-2 and human immune system, imbalance of proand anti-inflammatory cytokines, disruption of interferon production. However, this statement requires further research.

Risk factors for severity in seasonal respiratory viral infections and how they guide management in hematopoietic cell transplant recipients.

Seasonal respiratory virus infections (RVIs) often progress to severe diseases in hematopoietic cell transplant (HCT) recipients. This review summarizes the current evidence on risk factors for the severity of RVIs in this high-risk population and provides clinical management. The likelihood of the respiratory viral disease progression depends on the immune status of the host and the type of virus. Conventional host factors, such as the immunodeficiency scoring index and the severe immunodeficiency criteria, have been utilized to estimate the risk of progression to severe disease, including mortality. Recent reports have suggested nonconventional risk factors, such as hyperglycemia, hypoalbuminemia, prior use of antibiotics with broad anaerobic activity, posttransplant cyclophosphamide, and pulmonary impairment after RVIs. Identifying novel and modifiable risk factors is important with the advances of novel therapeutic and preventive interventions for RVIs. Validation of recently identified risk factors for severe RVIs in HCT recipients is required. The development of innovative interventions along with appropriate risk stratification is critical to improve outcomes in this vulnerable population.

One-fourth of COVID-19 patients have an impaired pulmonary function after 12 months of disease onset.

There is increasing data that show a persistently impaired pulmonary function upon recovery after severe infection. Little is known however about the extent, recovery and determinants of pulmonary impairment across the full spectrum of COVID-19 severity over time. In a well characterized, prospective cohort of both hospitalised and non-hospitalised individuals with SARS-CoV-2 infection, the RECoVERED study, pulmonary function (diffusing capacity for carbon monoxide (DLCO)) and spirometry) was measured until one year after disease onset. Additionally, data on sociodemographics, clinical characteristics, symptoms, and health-related quality of life (HRQL) were collected. Pulmonary function and these determinants were modelled over time using mixed-effect linear regression. Determinants of pulmonary function impairment at 12 months after disease onset were identified using logistic regression. Between May 2020 and December 2021, 301 of 349 participants underwent at least one pulmonary function test. After one year of follow-up, 25% of the participants had an impaired pulmonary function which translates in 11%, 22%, and 48% of the participants with mild, moderate and severe/critical COVID-19. Improvement in DLCO among the participants continued over the period across one, six and twelve months. Being older, having more than three comorbidities (p<0·001) and initial severe/critical disease (p<0·001) were associated with slower improvement of pulmonary function over time, adjusted for age and sex. HRQL improved over time and at 12 months was comparable to individuals without impaired pulmonary function. The prevalence of impaired pulmonary function after twelve months of follow-up, was still significant among those with initially moderate or severe/critical COVID-19. Pulmonary function increased over time in most of the severity groups. These data imply that guidelines regarding revalidation after COVID-19 should target individuals with moderate and severe/critical disease severities.

Clozapine for the treatment of aggressiveness and agitation in advanced dementia.

Distressing behavioural symptoms, particularly agitation and aggressiveness, remain a difficult problem in everyday clinical practice in the treatment of multimorbid patients with dementia. Clozapine may be an effective therapeutic alternative in this context. In a retrospective study, patients who had a diagnosis of dementia and had been treated in a specialized geriatric psychiatry unit with clozapine between August 2018 and February 2022 were included, and medical records were systematically reviewed. The Clinical Global Impressions Scale was used to assess improvement, and the Pittsburgh Agitation Scale for symptom reduction. In addition, side effects and clinical features were documented in detail. A total of 31 patients (median age 82 years) were identified with a mean clozapine dose of 47.2 (SD 35.6) mg. A total of 13 patients tolerated clozapine very well, 10 showed tolerable side effects, and in 10 patients side effects were the reason for stopping clozapine. Behavioural symptoms improved significantly, as indicated by the assessment scores. In summary, clozapine was effective and well tolerated in 23 patients, suggesting that low-dose clozapine may help to alleviate the suffering of difficult-to-treat multimorbid patients with advanced dementia and their caregivers. However, particular attention should be paid to adverse drug reactions, especially in patients with cardiovascular and pulmonary impairment.

Is there cardiac autonomic dysfunction in children and adolescents with exercise-induced bronchospasm?

ABSTRACT Background The pulmonary impairment in patients with bronchoconstriction induced by eucapnic voluntary hyperpnea(EVH) goes beyond the respiratory system, also impairing autonomic nervous modulation. This study aimed to evaluate the behavior of cardiac autonomic modulation in young asthmatics with and without EIB after the EVH test. Research design and methods A cross-sectional study design using 54 asthmatics(51.9% female), aged between 10 and 19 years, investigated with the EVH test. Forced expiratory volume in one second(FEV1) was measured at 5, 10, 15, and 30 min after EVH. Heart rate variability(HRV) measures of time were assessed pre and 30 min-post EVH. The diagnosis of Exercise-Induced bronchoconstriction with underlying clinical asthma(EIBA) was confirmed by a fall in FEV1 ≥10% compared to baseline. Results Thirty(55.5%) asthmatics had EIBA. Subjects with EIBA have reduced mean of the R-R intervals in relation to baseline until 15 minutes after EVH. Individuals without EIBA had increased parasympathetic activity compared to baseline(rMSSD) from 5 min after EVH(p < 0.05). This parasympathetic activity increase in relation to baseline was seen in individuals with EIBA after 25 minutes (rMSSD = 49.9 ± 5.3 vs 63.5 ± 7.2, p < 0.05). Conclusion Young asthmatics with EIBA present a delay in the increase of the parasympathetic component after EVH when compared to asthmatics without EIBA.

Exploring the mechanisms of long COVID: Insights from computational analysis of SARS-CoV-2 gene expression and symptom associations.

Long coronavirus disease(COVID) has emerged as a global health issue, affecting a substantial number of people worldwide. However, the underlying mechanisms that contribute to the persistence of symptoms in long COVID remain obscure, impeding the development of effective diagnostic and therapeutic interventions. In this study, we utilized computational methods to examine the gene expression profiles of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection and their associations with the wide range of symptoms observed in long COVID patients. Using a comprehensive data set comprising over 255 symptoms affecting multiple organ systems, we identified differentially expressed genesand investigated their functional similarity, leading to the identification of key genes with the potential to serve as biomarkers for long COVID. We identified the participation of hub genes associated with G-protein-coupled receptors (GPCRs), which are essential regulators of T-cell immunity and viral infection responses. Among the identified common genes were CTLA4, PTPN22, KIT, KRAS, NF1, RET, and CTNNB1, which play a crucial role in modulating T-cell immunity via GPCR and contribute to a variety of symptoms, including autoimmunity, cardiovascular disorders, dermatological manifestations, gastrointestinal complications, pulmonary impairments, reproductive and genitourinary dysfunctions, and endocrine abnormalities. GPCRs and associated genes are pivotal in immune regulation and cellular functions, and their dysregulation may contribute to the persistent immune responses, chronic inflammation, and tissue abnormalities observed in long COVID. Targeting GPCRs and their associated pathways could offer promising therapeutic strategies to manage symptoms and improve outcomes for those experiencing long COVID. However, the complex mechanisms underlying the condition require continued study to develop effective treatments. Our study has significant implications for understanding the molecular mechanisms underlying long COVID and for identifying potential therapeutic targets. In addition, we have developed a comprehensive website (https://longcovid.omicstutorials.com/) that provides a curated list of biomarker-identified genes and treatment recommendations for each specific disease, thereby facilitating informed clinical decision-making and improved patient management. Our study contributes to the understanding of this debilitating disease, paving the way for improved diagnostic precision, and individualized therapeutic interventions.