Comparison of clinical features of cystic fibrosis patients eligible but not on CFTR modulators to ineligible for CFTR modulators.

INTRODUCTION: Cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs target the underlying defect and improve CFTR function. They are a part of standard care in many countries, but not all patients are eligible for these drugs due to age and genotype. Here, we aimed to determine the characteristics of non-eligible patients for CFTR modulators in the CF registry of Turkey (CFRT) to highlight their clinical needs. METHODS: This retrospective cohort study included CF patient data from the CFRT in 2021. The decision of eligibility for the CFTR modulator was determined according to the 'Vertex treatment-Finder' on the Vertex® website. Demographic and clinical characteristics of patients were compared between eligible (group 1) and ineligible (group 2) groups for CFTR modulators. RESULTS: Among the study population (N = 1527), 873 (57.2%) were in group 1 and 654 (42.8%) were in group 2. There was no statistical difference between groups regarding sex, meconium ileus history, diagnoses via newborn screening, FEV1 z-score, CF-associated complications, organ transplant history, and death. Patients in group 2 had a higher incidence of pancreatic insufficiency (87.7% vs. 83.2%, p = .010), lower median height z-scores (-0.87 vs. -0.55, p < .001), lower median body mass index z-scores (-0.65 vs. -0.50, p < .001), longer days receiving antibiotics due to pulmonary exacerbation (0 [interquartile range, IQR: 0-2] vs. 0 [IQR: 0-7], p = 0.001), and more non-invasive ventilation support (2.6% vs. 0.9%, p = 0.008) than patients in group 1. CONCLUSION: The ineligible group had worse clinical outcomes than the eligible group. This highlights their need for life-changing drugs to improve clinical outcomes.

Management of iatrogenic airway bleeding with flexible bronchoscopy: Evidence or experience-based?

Iatrogenic bleeding during bronchoscopy may lead to early termination, insufficient sample collection, decreased diagnostic accuracy, and even death. Unlike rigid bronchoscopy, the management of bleeding during flexible fiberoptic bronchoscopy does not allow the use of methods such as cautery, direct pressure, etc. and is usually limited to the application of liquids. The management of endobronchial bleeding usually depends on two main mechanisms: 1) vasoconstriction; 2) enhancing coagulation to form fibrin clots. The data on cold saline, the most widely recognized agent, is based on case reports and the experience of centers, not randomized controlled trials. Vasoconstrictor agents consist of adrenaline, vasopressin analogues, phenylephrine, and xylometazoline hydrochloride. However, there are only a limited number of randomized controlled trials on adrenaline, and information on the remaining substances is limited to retrospective studies, case reports, and expert opinions. The endobronchial administration of tranexamic acid, which inhibits fibrin degradation, has been the subject of very few studies. Despite its documented efficacy, information regarding its dosage, frequency of use, and safety is lacking. Although Ankaferd Blood Stopper, which binds erythrocytes to the vascular endothelium, has been shown to be effective in controlling bleeding related to dental procedures, the gastrointestinal tract, and operations, only one retrospective study found it to be effective against endobronchial bleeding that could not be controlled with cold saline and adrenaline. Although there are a variety of agents that centers use in their routine procedures, there is not yet a consensus on the efficacy, dose, frequency, and safety of any of them.

An 8-year observational study of the death places of patients with COPD in Turkey.

AIM: The place of death is one of the indicators of the quality of end-of-life care, which has become an essential public health issue with the aging of the population and the increase in life expectancy. There is a lack of data regarding the location of deaths caused by chronic obstructive pulmonary disease (COPD), the third-leading cause of mortality worldwide. This retrospective, cross-sectional study aimed to investigate the places of death of patients with COPD in Turkey and their trends over the years. METHODS: The study included patients who had a COPD International Classification of Diseases code in the hospital information system and were provided a medication report for this disease in a university hospital's chest diseases outpatient clinic between January 1, 2014, and December 31, 2021. The place and date of death were obtained from the death notification system and recorded as an in-hospital or out-of-hospital death. RESULTS: A total of 1402 (77.3%) patients died in the hospital and 412 (22.7%) died outside the hospital, and when comparing the pandemic period and before, no significant difference was observed between the places of death. Sixty-three (49.6%) of 127 patients over the age of 90 years died outside the hospital, and a significant relationship was observed between advanced age and out-of-hospital mortality (P < 0.005). CONCLUSION: According to our findings, a substantial number of patients with COPD in Turkey die in hospitals. The insufficiency of nursing homes and lack of hospice care cause more hospital deaths. Our data are expected to guide the development of end-of-life care policies for patients with COPD in our country. Geriatr Gerontol Int 2023; 23: 938-944.

Lung cancer from suspicion to treatment: An indicator of healthcare access in Turkey.

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths worldwide. Before beginning lung cancer treatment, it is necessary to complete procedures such as suspecting lung cancer, obtaining a pathologic diagnosis, and staging. This study aimed to investigate the processes from suspicion of lung cancer to diagnosis, staging, and treatment initiation. METHODS: The study was designed as a multicenter and cross-sectional study. Patients with lung cancer from various health institutions located in all geographic regions of Turkey were included in the study. The sociodemographic and clinical characteristics of the patients, the characteristics of the health institutions and geographic regions, and other variables of the lung cancer process were recorded. The time from suspicion of lung cancer to pathologic diagnosis, radiologic staging, and treatment initiation, as well as influencing factors, were investigated. RESULTS: The study included 1410 patients from 29 different medical centers. The mean time from the initial suspicion of lung cancer to the pathologic diagnosis was 48.0 ± 52.6 days, 39.0 ± 52.7 days for radiologic staging, and 74.9 ± 65.5 days for treatment initiation. The residential areas with the most suspected lung cancer cases were highly developed socioeconomic zones. Primary healthcare services accounted for only 0.4% of patients with suspected lung cancer. The time to pathologic diagnosis was longer in the Marmara region, and the wait time for staging and treatment initiation was longer in Eastern and Southeastern Anatolia. Patients who presented to chest disease referral hospitals with peripheral lesions, those with early-stage disease, and those who were diagnosed surgically had significantly longer wait times. CONCLUSION: The time between pathologic diagnosis, staging, and treatment initiation in lung cancer was longer than expected. Increasing the role of primary healthcare services and distributing socioeconomic resources more equally will contribute to shortening the time to diagnosis and improve treatment processes for lung cancer.

Necrotizing pneumonia due to Aspergillus and Salmonella after immune checkpoint inhibitor treatment: An unusual case and review of the literature.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are a promising new treatment for different types of cancer. The infectious complications in patients taking ICIs are rare. CASE REPORT: A 58-year-old male who received chemotherapy consisting of pembrolizumab (PD-1 inhibitor) for esophagus squamous cell carcinoma one month before was admitted to the emergency room with shortness of breath soon after fiberoptic bronchoscopy, which was done for the inspection of the lower airway. A computed tomography of the chest revealed a progressive consolidation on the right upper lobe. Salmonella group D was isolated from the bronchoalveolar lavage (BAL) fluid culture. The fungal culture of the same clinical sample yielded Aspergillus niger; furthermore, a high titer (above the cut-off values) of Aspergillus antigen was found both in the BAL fluid and serum of the patient. Despite the effective spectrum and appropriate dose of antimicrobial treatment, the patient died due to disseminated intravascular coagulopathy. CONCLUSIONS: Awareness of unusual pathogens in the etiology of pneumonia after ICI treatment may help to avoid underdiagnosis.

The association of antiviral drugs with COVID-19 morbidity: The retrospective analysis of a nationwide COVID-19 cohort.

Background and objectives: Although several repurposed antiviral drugs have been used for the treatment of COVID-19, only a few such as remdesivir and molnupiravir have shown promising effects. The objectives of our study were to investigate the association of repurposed antiviral drugs with COVID-19 morbidity. Methods: Patients admitted to 26 different hospitals located in 16 different provinces between March 11-July 18, 2020, were enrolled. Case definition was based on WHO criteria. Patients were managed according to the guidelines by Scientific Board of Ministry of Health of Turkey. Primary outcomes were length of hospitalization, intensive care unit (ICU) requirement, and intubation. Results: We retrospectively evaluated 1,472 COVID-19 adult patients; 57.1% were men (mean age = 51.9 ± 17.7years). A total of 210 (14.3%) had severe pneumonia, 115 (7.8%) were admitted to ICUs, and 69 (4.7%) were intubated during hospitalization. The median (interquartile range) of duration of hospitalization, including ICU admission, was 7 (5-12) days. Favipiravir (n = 328), lopinavir/ritonavir (n = 55), and oseltamivir (n = 761) were administered as antiviral agents, and hydroxychloroquine (HCQ, n = 1,382) and azithromycin (n = 738) were used for their immunomodulatory activity. Lopinavir/ritonavir (ß [95% CI]: 4.71 [2.31-7.11]; p = 0.001), favipiravir (ß [95% CI]: 3.55 [2.56-4.55]; p = 0.001) and HCQ (ß [95% CI]: 0.84 [0.02-1.67]; p = 0.046) were associated with increased risk of lengthy hospital stays. Furthermore, favipiravir was associated with increased risks of ICU admission (OR [95% CI]: 3.02 [1.70-5.35]; p = 0.001) and invasive mechanical ventilation requirement (OR [95% CI]: 2.94 [1.28-6.75]; p = 0.011). Conclusion: Our findings demonstrated that antiviral drugs including lopinavir, ritonavir, and favipiravir were associated with negative clinical outcomes such as increased risks for lengthy hospital stay, ICU admission, and invasive mechanical ventilation requirement. Therefore, repurposing such agents without proven clinical evidence might not be the best approach for COVID-19 treatment.

A basic tool to determine exercise capacity in COPD: 4-meter gait speed.

Introduction: Determination of exercise capacity is crucial for chronic obstructive pulmonary disease (COPD) management since it is an indicator of life quality and mortality. Various previously defined tests, including the cardiopulmonary exercise test (CPET), the 6-minute walking test (6MWT), and the incremental shuttle walk test, are used to determine COPD patients' exercise capacity. However, they all have some disadvantages, such as time, personnel, and equipment requirements, limiting their daily practice use. Here, it was aimed to investigate the role of 4-meter gait speed (4mGS) in evaluating exercise capacity in COPD. Materials and Methods: We included 40-to-70-year-old COPD patients with no contraindications for exercise testing. We performed the tests at standard intervals without affecting each other's results. We also performed spirometry. We used the modified Medical Research Council Scale, COPD Assessment Test, and BODE index to determine the current status of individuals. Result: Twenty-three (female/male= 2/21) subjects aged 58.1 ± 7.3 were included in the study. A statistically significant correlation was observed between 4mGS and peak VO2 values. There was also a statistically significant relationship between 4mGS and 6MWT distance. 4mGS correlated with CAT and BODE scores to represent the general medical status of patients. Conclusions: Considering its easy applicability and reproducibility, 4mGS seems to be a strong candidate for daily clinical use in monitoring the exercise capacity of COPD patients. Further studies in larger patient groups are needed to support these results.

Ultrasound Assessment of Sarcopenia in Patients With Sarcoidosis.

OBJECTIVES: Sarcoidosis can cause sarcopenia like other chronic diseases. Ultrasonography is a simple method, which has been used frequently in recent years. We aimed to evaluate the sarcoidosis patients with ultrasonography for sarcopenia and to compare the results of ultrasonography with the accepted standard method, bioelectrical impedance analysis (BIA). METHODS: BIA and handgrip test were applied to all patients diagnosed with sarcoidosis. The patients were classified according to the presence of probable sarcopenia with their handgrip results and the presence of sarcopenia with the appendicular skeletal muscle mass index calculated with using BIA. Ultrasonography was applied to each patient and the thickness of seven different muscle groups of the patients were evaluated. The ability of muscle thickness values measured by ultrasonography to predict sarcopenia was compared with the reference standard test BIA. RESULTS: Forty patients (women/men = 31/9) were included in our study. The mean age was 53.2 ± 12.5 years. A statistically significant positive correlation was observed between handgrip strength and gastrocnemius medialis (GM), rectus femoris (RF) cross-sectional area, rectus abdominis (RA), external oblique (EO), transversus abdominus (TA), and diaphragm thicknesses. Therefore, there was a significant correlation between fat free mass index with RA, EO, and TA muscles. According to the ROC analysis, statistically significant muscle groups predicting sarcopenia were found as GM, RF cross-sectional area, EO, and IO. Again, according to the ROC analysis, it was seen that the thicknesses of GM, RA, EO, IO, and TA muscles corrected for BMI predicted probable sarcopenia with quite high sensitivity and specificity. CONCLUSIONS: Muscle thicknesses measured by ultrasonography are helpful for the diagnosis of sarcopenia that may develop in chronic diseases such as sarcoidosis. Further studies with higher number of patients are needed to validate the results of the present pilot study.

Is there any contribution of bronchial washing to biopsy in the diagnosis of patients with endobronchial pathology in the era of personalized medicine?

INTRODUCTION: Bronchoscopic biopsies and bronchial washings (BW) are commonly used together for the diagnosis of centrally located tumors. This study aimed to investigate the clinical relevance of routinely collecting BWs in patients who simultaneously had biopsies for visible endobronchial lesions in the current molecular analysis-driven personalized medicine era. MATERIALS AND METHODS: We retrospectively reviewed the patients who underwent fiberoptic bronchoscopy (FOB) between October 2011 and December 2016. Patients who had both BW and biopsy specimens (EBB: endobronchial forceps biopsy and/or EBNA: endobronchial needle aspiration biopsy) for visible endobronchial lesions were included in this study. Demographic and clinical data, macroscopic findings during FOB, pathology results, and final diagnoses were collected from the hospital database. RESULT: The study included 269 patients (220 males/49 females) with a mean age of 61.6 ± 10.6 years. While the overall diagnostic yield of FOB was 71.4%, the diagnostic yields of bronchoscopic procedures were 68.2% for EBB, 83.3% for EBNA, and 19.7% for BW. Only three patients (1.1%) with undiagnostic biopsies had positive BW cytology revealing merely malignant epithelial cells. CONCLUSIONS: BW provided a negligible diagnostic contribution in 1.1% (n= 3) of the patients. These three patients had undergone further diagnostic procedures for making a proper therapeutic management plan. In the era of personalized therapy, it is logical to obtain more biopsy in the time spent for BWs.

The predictors of COVID-19 mortality in a nationwide cohort of Turkish patients.

The COVID-19-related death rate varies between countries and is affected by various risk factors. This multicenter registry study was designed to evaluate the mortality rate and the related risk factors in Turkey. We retrospectively evaluated 1500 adults with COVID-19 from 26 centers who were hospitalized between March 11 and July 31, 2020. In the study group, 1041 and 459 cases were diagnosed as definite and highly probable cases, respectively. There were 993 PCR-positive cases (66.2%). Among all cases, 1144 (76.3%) were diagnosed with non-severe pneumonia, whereas 212 (14.1%) had severe pneumonia. Death occurred in 67 patients, corresponding to a mortality rate of 4.5% (95% CI:3.5-5.6). The univariate analysis demonstrated that various factors, including male sex, age ≥65 years and the presence of dyspnea or confusion, malignity, chronic obstructive lung disease, interstitial lung disease, immunosuppressive conditions, severe pneumonia, multiorgan dysfunction, and sepsis, were positively associated with mortality. Favipiravir, hydroxychloroquine and azithromycin were not associated with survival. Following multivariate analysis, male sex, severe pneumonia, multiorgan dysfunction, malignancy, sepsis and interstitial lung diseases were found to be independent risk factors for mortality. Among the biomarkers, procalcitonin levels on the 3rd-5th days of admission showed the strongest associations with mortality (OR: 6.18; 1.6-23.93). This study demonstrated that the mortality rate in hospitalized patients in the early phase of the COVID-19 pandemic was a serious threat and that those patients with male sex, severe pneumonia, multiorgan dysfunction, malignancy, sepsis and interstitial lung diseases were at increased risk of mortality; therefore, such patients should be closely monitored.

Pulmonary manifestations of antiphospholipid syndrome: a retrospective analysis of 67 patients.

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by arterial and/ or venous thrombosis accompanied by persistently elevated levels of antiphospholipid antibodies (aPLs). The aim of this study is to evaluate the pulmonary manifestations of APS and compare the levels of aPLs in patients with and without pulmonary involvement. We retrospectively reviewed the files of patients with the diagnosis of APS between October 2010 and May 2017. Demographic data, clinical, radiological and laboratory findings were recorded. The study included 67 patients (56 female/11 male) with a mean age of 39 ± 13 years. Pulmonary manifestations such as parenchymal and/or vascular involvement were seen in 12 (17.9%) patients. The patients with and without pulmonary manifestations were not significantly different in terms of age (p = 0.46), comorbidities (p = 0.48) and APS duration (p = 0.66). Acute pulmonary thromboembolism (PE) was determined in 11 (16.4%), alveolar hemorrhage in 2 (3%) patients. Four patients with acute PE (36%) developed chronic thromboembolic pulmonary hypertension (CTEPH). One patient developed both CTEPH and diffuse alveolar hemorrhage after acute PE during follow up. Antiphosholipid antibody IgM was highly positive in patients with PE compared to patients without PE (p = 0.005). Other antibodies and lupus anticoagulant were not significantly different in patients with and without PE. None of the patients were deceased due to pulmonary manifestations of APS. PE was the most common pulmonary manifestation of APS. The development of CTEPH was high among APS patients. Patients with APS should be closely followed for the onset of PE and CTEPH.

Covid-19: The Biggest Threat of the 21st Century: In Respectful Memory of the Warriors All Over the World.

Since the first case was diagnosed in China, the new coronavirus infection (COVID-19) has become the number one issue in the world and it seems to remain trend-topic for a long time. Until 17 April, it affected 210 countries, infected over 2 million people and caused approximately 150000 deaths. Although the course of the disease ranges from asymptomatic state to severe ARDS; the majority of patients reveal only mild symptoms. Though adults are the most commonly affected group; it can also be seen in newborns and elderly patients. Unfortunately, elderly patients are the most vulnerable group with higher mortality. Elderly patients, smokers and patients with comorbid conditions are most affected by the disease. In certain diagnostical tool is the real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) test. However, it can be resulted in false-negative results and in this case the computed thorax tomography (CT) is one of the most important tools with high sensitivity. Besides the supportive treatment, most commonly used agents are immunomodulatory drugs such as plaquenil and azitromycin, and anti-virals including oseltamivir, ritonavir-lopinavir, favipiravir. Until a vaccine or a specific therapy invented, the most important intervention to control the disease is to fight against transmission. This is a real war and the doctors are the soldiers.

What We Learned about COVID-19 So Far? Notes from Underground.

The novel coronavirus pandemic poses a major global threat to public health. Our knowledge concerning every aspect of COVID-19 is evolving rapidly, given the increasing data from all over the world. In this narrative review, the Turkish Thoracic Society Early Career Taskforce members aimed to provide a summary on recent literature regarding epidemiology, clinical findings, diagnosis, treatment, prevention, and control of COVID-19. Studies revealed that the genetic sequence of the novel coronavirus showed significant identity to SARS-CoV and MERS-CoV. Angiotensin-converting enzyme 2 receptor is an important target of the SARS-CoV-2 while entering an organism. Smokers were more likely to develop the disease and have a higher risk for ICU admission. The mean incubation period was 6.4 days, whereas asymptomatic transmission was reported up to 25 days after infection. Fever and cough were the most common symptoms, and cardiovascular diseases and hypertension were reported to be the most common comorbidities among patients. Clinical manifestations range from asymptomatic and mild disease to severe acute respiratory distress syndrome. Several patients showed typical symptoms and radiological changes with negative RT-PCR but positive IgG and IgM antibodies. Although radiological findings may vary, bilateral, peripherally distributed, ground-glass opacities were typical of COVID-19. Poor prognosis was associated with older age, higher Sequential Organ Failure Assessment score, and high D-dimer level. Chloroquine was found to be effective in reducing viral replication in vitro. Likewise, protease inhibitors, including lopinavir/ritonavir, favipiravir, and nucleoside analogue remdesivir were proposed to be the potential drug candidates in COVID-19 management. Despite these efforts, we still have much to learn regarding the transmission, treatment, and prevention of COVID-19.

The contribution of bronchoalveolar lavage in the diagnosis of welder's lung in a patient with pulmonary fibrosis.

Interstitial pulmonary fibrosis is rare clinical entity related to welding usually associated with long term and heavy exposure to welding fumes. A 56-year-old asymptomatic male patient was referred to our clinic due to abnormal chest X-ray findings that was requested for regular controls. He has been working as a welder both indoor and outdoor settings for the last 25 years. The radiological findings were compatible with usual interstitial pneumonia on computed tomography of thorax. Pulmonary function tests, exercise capacity and laboratory results were within normal limits. Collagen tissue markers were negative. In order to confirm the relation of welding with pulmonary fibrosis, bronchoalveolar lavage was performed and stained with Prussian blue. The demonstration of hemosiderin-laden macrophages (25%) confirmed this association and allowed differential diagnosis. Besides it helped the patient decide to leave his job.

Diagnostic utility of conventional transbronchial needle aspiration in older patients.

BACKGROUND: In older patients, diagnosis and initial treatment should be considered as soon as possible because of high disease burden and complications. Conventional transbronchial needle aspiration (C-TBNA) is an important and safe method for the diagnosis of mediastinal lesions and staging lung cancer in the general population. We aimed to evaluate the diagnostic utility and complications of C-TBNA procedure in older patients aged ≥ 65 years. METHOD: We retrospectively evaluated C-TBNA results consecutively. Demographic data, clinical, radiological and flexible bronchoscopy (FB) findings, complications during C-TBNA and incidence of diagnostic C-TBNA with the presence of abundant lymphoid cells of polymorphous appearance both in patients aged ≥ 65 years and in younger patients were determined. RESULTS: C-TBNA was performed to a total of 317 patients, including 109 older and 208 younger patients attended to our clinic between 2012 and 2016. The mean ages of older and younger patients were 70.3 ± 4.6 and 52.5 ± 10 years, respectively (p < 0.001). Overall, 75.2% of older and 80.3% of younger patients had diagnostic C-TBNA. The diagnostic utility of C-TBNA did not differ significantly between older and younger patients (p = 0.297). During C-TBNA, one older patient had a complication of bronchospasm, and four younger patients had complications such as bleeding (n = 1) and bronchospasm (n = 3). There was no statistically significant difference between older and younger patients in terms of complications during C-TBNA procedure (p = 0.49). CONCLUSION: C-TBNA is a safe procedure with similar diagnostic yield in older patients.