A Narrative Review of the Clinical Trials in Sleep-Related Breathing Disorders from 2022 to Present.

Sleep-related breathing disorders (SRBD) comprise obstructive sleep apnea (OSA), central sleep apnea (CSA), obesity-hypoventilation syndrome (OHS), as well as isolated sleep-related hypoxemia (ISRH), according to the recent International Classification of Sleep Disorders 3. During the last decades, there have been cumulative research reports indicating an association between the SRBD and increased cardiometabolic illness and death, as well as decreased quality of life. Notwithstanding, the results have been inconclusive, and the evidence level was not high regarding the effect of treatment for the SRBD on adverse outcomes. In the current work, we aim to give a comprehensive review of the clinical trials published from January 2022 to August 31, 2023. We highlight the heterogeneity of cardiometabolic disorders among adults with SRBD and particularly emphasize OSA management, drug therapy for OSA, positive airway pressure (PAP) therapy and cardiovascular outcomes, other effects of PAP in pregnancy and neurocognitive function, as well as the effects of surgical treatment and oral appliances. We also underline future directions in OSA management, telemonitoring, and druginduced sleep endoscopy in managing the SRBD, especially OSA. We ascertain that more studies are needed within the CSA, OHS, and ISRH research fields.

ERS clinical practice guidelines: high-flow nasal cannula in acute respiratory failure.

BACKGROUND: High-flow nasal cannula (HFNC) has become a frequently used noninvasive form of respiratory support in acute settings; however, evidence supporting its use has only recently emerged. These guidelines provide evidence-based recommendations for the use of HFNC alongside other noninvasive forms of respiratory support in adults with acute respiratory failure (ARF). MATERIALS AND METHODOLOGY: The European Respiratory Society task force panel included expert clinicians and methodologists in pulmonology and intensive care medicine. The task force used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methods to summarise evidence and develop clinical recommendations for the use of HFNC alongside conventional oxygen therapy (COT) and noninvasive ventilation (NIV) for the management of adults in acute settings with ARF. RESULTS: The task force developed eight conditional recommendations, suggesting the use of 1) HFNC over COT in hypoxaemic ARF; 2) HFNC over NIV in hypoxaemic ARF; 3) HFNC over COT during breaks from NIV; 4) either HFNC or COT in post-operative patients at low risk of pulmonary complications; 5) either HFNC or NIV in post-operative patients at high risk of pulmonary complications; 6) HFNC over COT in nonsurgical patients at low risk of extubation failure; 7) NIV over HFNC for patients at high risk of extubation failure unless there are relative or absolute contraindications to NIV; and 8) trialling NIV prior to use of HFNC in patients with COPD and hypercapnic ARF. CONCLUSIONS: HFNC is a valuable intervention in adults with ARF. These conditional recommendations can assist clinicians in choosing the most appropriate form of noninvasive respiratory support to provide to patients in different acute settings.

Altered pulmonary functions due to biomass smoke in a rural population of Turkish women: a descriptive study.

INTRODUCTION: Wood or other organic sources of fuel are used as source of energy for heating or cooking particularly in developing countries. The aim of the current study was to evaluate the association between biomass exposure time and parameters of pulmonary function tests. MATERIALS AND METHODS: Four hundred twenty-four consecutive women who lived and exposed to biomass smoke in a small province in Eastern Turkey were involved. This study was performed with women who had come to pulmonology out-patient clinic with symptom of dyspnea. RESULT: The independent variables assessed in the study patients were age, BMI, starting age of cooking, hours per day and weeks per month spent cooking, and cooking years; the dependent variables were PFT parameters. Ninety-two (21.6%) patients had an obstructive PFT pattern. Sixty-seven (73%) of these patients were classified as GOLD 2 and 25 (27%) patients were classified as GOLD 3. Seventy-five (17.6 %) of the patients had restrictive lung disease; 54 (72%) of these patients were found to have a mild and 21 (27%) had a moderate restrictive pattern. Increased number of years in cooking and to start cooking at younger ages were a risk factors for the development of obstructive and restrictive disease. There was a statistically significant and negative correlation between increased number of years and the value of FEV1 (r= -0.917; p=< 0.001), FEV1/FVC (r= -0.739; p< 0.001), and FVC (r= -0.906; p< 0.001). The median time of cooking required was 23 years for the development of obstruction, and 25 years for restriction, respectively. CONCLUSIONS: Cumulative biomass exposure time is associated with impairment in PFT parameters; results in both obstructive and restrictive lung disease. Biomass exposure is a public health problem and pre-cautions should be taken in order to prevent impaired pulmonary functions.

Epidemiology of NIV for Acute Respiratory Failure in COPD Patients: Results from the International Surveys vs. the "Real World".

Non-invasive ventilation (NIV) has been recommended as the  first-line ventilation modality for acute respiratory failure (ARF) due to acute exacerbation of chronic obstructive pulmonary disease (AECOPD) based on strong evidence. However, everyday clinical practice may differ from findings of multiple randomized controlled trials. Physicians and respiratory therapists involved in NIV management have been queried about its utilization and effectiveness. In addition to these estimates, cohort studies and analysis of large inpatient dataset of patients with AECOPD and ARF managed with NIV have been extensively published over the last two decades. This review summarizes the perception of medical staff vs. the "real life" data about NIV use for ARF in AECOPD patients.

Approach of pulmonologists in Turkey to noninvasive mechanical ventilation use at home for chronic respiratory failure.

INTRODUCTION: To define approach of pulmonologists in Turkey to noninvasive mechanical ventilation (NIV) use for chronic respiratory failure (CRF), the most currently applied technique for home mechanical ventilation. PATIENTS AND METHODS: A 38-question survey, developed and tested by the authors, was distributed throughout Turkey to 2205 pulmonologists by e-mail. RESULT: Twenty-seven percent of the pulmonologists responded (n=596). Domiciliary NIV was reported to be prescribed by 340 physicians [57.1% of all responders and 81% of pulmonologists practicing NIV at clinical practice (n= 420)]. NIV prescription was associated with physician's title, type of hospital, duration of medical license, total number of patients treated with NIV during residency and current number of patients treated with NIV per week (p< 0.05). Main estimated indications were listed as chronic obstructive pulmonary disease (median, 25-75 percentile of the prescriptions: 75%, 60-85), obesity hypoventilation syndrome (10%, 2-15), overlap syndrome (10%, 0-20) and restrictive lung disease (5%, 2-10). For utilization of NIV at home, Bilevel positive airway pressure-spontaneous mode (40%, 0-80) and oronasal mask (90%, 60-100) were stated as the most frequently recommended mode and interface, respectively. Pressure settings were most often titrated based on arterial blood gas findings (79.2%). Humidifier was stated not to be prescribed by approximately half of the physicians recommending domicilliary NIV, and the main reason for this (59.2%) was being un-refundable by social security foundation. CONCLUSION: There is a wide variation in Turkey for prescription of NIV, which is supposed to improve clinical course of patients with CRF. Further studies are required to determine the possible causes of these differences, frequency of use and patient outcomes in this setting.

Use and Outcomes of Noninvasive Ventilation for Acute Respiratory Failure in Different Age Groups.

BACKGROUND: The prevalence of chronic disease and do-not-intubate status increases with age. Thus, we aimed to determine characteristics and outcomes associated with noninvasive ventilation (NIV) use for acute respiratory failure (ARF) in different age groups. METHODS: A database comprising prospective data collected on site on all adult patients with ARF requiring ventilatory support from 8 acute care hospitals in Massachusetts was used. RESULTS: From a total of 1,225 ventilator starts, overall NIV utilization, success, and in-hospital mortality rates were 22, 54, and 18% in younger (18-44 y); 34, 65, and 13% in middle-aged (45-64 y); 49, 68, and 17% in elderly (65-79 y); and 47, 76, and 24% in aged (≥ 80 y) groups, respectively (P < .001, P = .08, and P = .11, respectively). NIV use for cardiogenic pulmonary edema and subjects with a do-not-intubate order increased significantly with advancing age (25, 57, 57, and 74% and 7, 12, 18, and 31%, respectively, in the 4 age groups [P < .001 and P = .046, respectively]). For subjects receiving NIV with a do-not-intubate order, success and in-hospital mortality rates were similar in different age groups (P = .27 and P = .98, respectively). CONCLUSIONS: NIV use and a do-not-intubate status are more frequent in subjects with ARF ≥ 65 y than in those <65 y, especially for subjects with cardiogenic pulmonary edema. However, NIV success and mortality rates were similar between age groups. (ClinicalTrials.gov registration NCT00458926.).

Where is Noninvasive Ventilation Actually Delivered for Acute Respiratory Failure?

PURPOSE: Few studies have examined locations of noninvasive ventilation (NIV) application for acute respiratory failure (ARF). We aimed to track actual locations of NIV delivery and related outcomes. METHODS: Observational cohort study based at 8 acute care hospitals in Massachusetts on adult patients admitted for ARF requiring ventilatory support during pre-determined time intervals. RESULTS: Of 1225 ventilator starts, 499 were NIV; 209 (42%) in intensive care units (ICU), 185 (37%) in emergency departments (ED), 91 (18%) on general wards, and 14 (3%) in other units. Utilization (% of all ventilator starts) (1), success (2) and in-hospital mortality (3) rates for patients initiated on NIV in ICU, ED, and general and other wards were (1) 38, 36, 73, and 52%, (2) 60, 77, 68, and 93% and (3) 25, 12, 17, and 0%, respectively (p < 0.05 for all). Patients with acute-on-chronic lung disease (ACLD) and acute pulmonary edema (APE) were begun on NIV most often in EDs and patients with 'de novo' ARF and neurologic disorders most often in ICU's. Approximately 2/3 of patients begun on NIV outside of ICUs were transferred within 72 h to ICUs, wards or other units. CONCLUSIONS: Most NIV starts occurred in ICUs and EDs but utilization rate was highest (>50%) on general wards where a fifth of NIV starts took place. Actual location depended on etiology of ARF as patients with ACLD and APE were started more often in EDs and "de novo" ARF in ICU. NIV failure and mortality rates were higher in ICUs related to the greater proportion of patients with "de novo" ARF.

A 10-year experience of tuberculosis in solid-organ transplant recipients.

OBJECTIVES: Tuberculosis remains an important problem in solid-organ transplant patients due to their immunocompromised state. The objective of the present study was to report the incidence, demographic characteristics, and various presentations of tuberculosis in solid-organ transplant recipients. MATERIALS AND METHODS: We evaluated a total of 999 patients (male/female = 665/334, 661 renal and 338 liver transplants) who underwent solid-organ transplant between 2003 and 2013. The medical records of all patients were retrospectively reviewed. Patients' demographics, transplant type, primary site of tuberculosis specimen culture and pathology results, chest radiograph, and thoracic computed tomography findings, total blood count and chemistry were all recorded. RESULTS: Among the 999 subjects, 19 patients (1.9%) (male/female: 15/4, mean ± SD age, 42 ± 18.5 y) were diagnosed with tuberculosis. The majority of patients (85%) were diagnosed with tuberculosis within 6 months after transplant, and 15% were diagnosed within 3 months. Most diagnoses of tuberculosis were based on histopathologic examination of biopsy material. Of these patients, 9 were diagnosed with pulmonary tuberculosis, 8 had extrapulmonary tuberculosis, and 2 had both. Nontuberculosis mycobacteria infections were detected in 3 patients. CONCLUSIONS: Even with a negative exposure history, tuberculosis can manifest as different clinic presentations in solid-organ transplant patients on immunosuppressive drugs, particularly in the first 6 months after transplant. Therefore, clinicians should always consider tuberculosis as the potential cause of an infectious disease with unknown cause to successfully diagnose and manage solid-organ transplant recipients.

Long-term risk of pulmonary embolism in solid-organ transplant recipients.

OBJECTIVES: Solid-organ transplant recipients can develop chronic hypercoagulation that increases the incidence of pulmonary embolism. Here, we evaluate the frequency of pulmonary embolism in solid-organ transplant recipients during the first 10 years after transplantation and evaluate the risk factors for its development. MATERIALS AND METHODS: The medical records of solid-organ transplant recipients who were treated between 2003 and 2013 were retrospectively reviewed. The reviewed data included demographics, type of transplant, comorbidities, procoagulation factors, thromboembolism prophylaxis, and the timing and extent of pulmonary embolism. RESULTS: In total, 999 solid-organ transplant recipients are included in this study (661 renal and 338 liver transplant recipients) (male: female ratio = 665:334). Twelve renal (1.2%) and 1 liver transplant recipient (0.3%) were diagnosed with pulmonary embolism. Pulmonary embolism developed 1 year after transplantation in 10 patients: 1 patient developed pulmonary embolism < 3 months after transplantation, and the other 9 patients developed pulmonary embolism within 3 to 6 months. No patients had a prior history of deep venous thrombosis or pulmonary embolism. Five patients received tacrolimus, 7 patients received sirolimus, and 1 patient received cyclosporine. Ten patients received prednisolone, and 8 patients received mycophenolate mofetil. All patients were homozygous normal for factor V Leiden and prothrombin genes. One patient was homozygous abnormal, and 1 patient had a heterozygous mutation in the methylenetetrahydrofolate reductase gene. Two patients were treated with low-molecular-weight heparin, while the remaining patients received warfarin. Eight patients were treated for 6 months, and the remainder received longer treatments. CONCLUSIONS: Here, the incidence of pulmonary embolism in solid-organ transplant recipients is 1.2%. Renal transplant recipients are at higher risk of developing pulmonary embolism than liver transplant recipients. The factors that increase the risk of pulmonary embolism in solid-organ transplant recipients appear to be multifactorial and include genetic predisposition.

Approach of pulmonologists in Turkey to noninvasive mechanical ventilation use in acute respiratory failure.

INTRODUCTION: Noninvasive mechanical ventilation (NIV) has been increasingly used worldwide for acute respiratory failure (ARF), especially in patients with chronic lung disorders. We aimed to define the approach of pulmonologists in Turkey to NIV use for ARF management. MATERIALS AND METHODS: A 38-question survey, developed and tested by authors, was distributed by e-mail to a total of 2.205 pulmonologists in Turkey. RESULT: Response rate was 27% (n= 596). Seventy-one percent of responders were practicing NIV in clinic. NIV use was found to be associated with responder's academic title, age, duration of medical license, type of physician's hospital and its region, patient load, NIV experience during residency, and duration of NIV and intensive care unit (ICU) experience (p< 0.001). Based on sub-group analysis of responders using NIV, median number of NIV patients followed-up per week was 4 [interquartile range (IQR): 2-6]. Most of the NIV users reported employment of wards (90%) and/or ICUs (86%) to follow-up patients, while 8.4% of the responders were applying NIV only in ICU's. Chronic obstructive lung disease (COPD) (99.5%), obesity hypoventilation syndrome (93.7%) and restrictive lung disease (89.4%) were the most common indications. Majority of NIV users (87%) were applying NIV to > 60% of patients with COPD, and success rate in COPD was reported as over 60% by 93% of users. Oronasal mask (median and IQR 90, 80-100%, respectively) and home care NIV ventilators (median and IQR 50, 10-85%, respectively) were the most commonly utilized equipment. CONCLUSIONS: NIV use in ARF varies based on hospital type, region and, especially, experience of the physician. Although consistent with guidelines and general practice, NIV use can still be improved and increased.

Cardiotoxicity following cyclophosphamidetherapy: a case report.

INTRODUCTION: Cardiac toxicity is one of the life-threatening complications of cancer therapy. Systemic anticancer treatments may exert their own toxic effects or can aggravate adverse effects of other drugs. We report a case of cyclophosphamide-induced cardiotoxicity in a patient with normal cardiac functions before chemotherapy. CASE PRESENTATION: A 66-year-old Caucasian woman with a mediastinal mass diagnosed with Burkitt lymphoma underwent chemotherapy with rituximab-hyperfractionated-cyclophosphamide-vincristine-doxorubicin-dexamethasone. On the seventh day of chemotherapy, she developed dyspnea. An electrocardiogram demonstrated low voltage in the limb and precordial leads. It also showed diffusely increased myocardial echogenicity, mild pericardial and pleural effusion, generally impaired biventricular systolic functions with a left ventricular ejection fraction of 31%, and right ventricular mid-apical akinesia, even though she had normal biventricular functions before chemotherapy. Cyclophosphamide-induced cardiotoxicity was suspected and she was given treatment for congestive heart failure. Her dyspnea decreased and she was discharged on the tenth day with a left ventricular ejection fraction of 37% and normal right ventricular function. After 1 month, echocardiography showed normal biventricular functions with a left ventricular ejection fraction of 60%. CONCLUSIONS: Drug-induced cardiotoxicity, therefore, should be taken into consideration when using cyclophosphamide therapy, especially when anthracyclines are co-administered. Close communication between hematologists and cardiologists is required.

Use and outcomes of noninvasive positive pressure ventilation in acute care hospitals in Massachusetts.

BACKGROUND: This study determined actual utilization rates and outcomes of noninvasive positive pressure ventilation (NIV) at selected hospitals that had participated in a prior survey on NIV use. METHODS: This observational cohort study, based at eight acute care hospitals in Massachusetts, focused on all adult patients requiring ventilatory support for acute respiratory failure during predetermined time intervals. RESULTS: Of 548 ventilator starts, 337 (61.5%) were for invasive mechanical ventilation and 211 (38.5%) were for NIV, with an overall NIV success rate of 73.9% (ie, avoidance of intubation or death while on NIV or within 48 h of discontinuation). Causal diagnoses for respiratory failure were classified as (I) acute-on-chronic lung disease (23.5%), (II) acute de novo respiratory failure (17.9%), (III) neurologic disorders (19%), (IV) cardiogenic pulmonary edema (16.8%), (V) cardiopulmonary arrest (12.2%), and (VI) others (10.6%). NIV use and success rates for each of the causal diagnoses were, respectively, (I) 76.7% and 75.8%, (II) 37.8% and 62.2%, (III) 1.9% and 100%, (IV) 68.5% and 79.4%, (V) none, and (VI) 17.2% and 60%. Hospital mortality rate was higher in patients with invasive mechanical ventilation than in patients with NIV (30.3% vs 16.6%, P < .001). CONCLUSIONS: NIV occupies an important role in the management of acute respiratory failure in acute care hospitals in selected US hospitals and is being used for a large majority of patients with acute-on-chronic respiratory failure and acute cardiogenic pulmonary edema. NIV use appears to have increased substantially in selected US hospitals over the past decade. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00458926; URL: www.clinicaltrials.gov.