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.

Patients with cystic fibrosis who could not receive the CFTR modulator treatment: What did they lose in 1 year?

BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disorder caused by CF transmembrane conductance regulator (CFTR) genetic variants. CFTR modulators improve pulmonary function and reduce respiratory infections in CF. This study investigated the clinical and laboratory follow-up parameters over 1 year in patients with CF who could not receive this treatment. METHODS: This retrospective cohort study included 2018 and 2019 CF patient data from the CF registry of Turkey. Demographic and clinical characteristics of 294 patients were assessed, who had modulator treatment indications in 2018 but could not reach the treatment. RESULTS: In 2019, patients younger than 18 years had significantly lower BMI z-scores than in 2018. During the 1-year follow-up, forced expiratory volumes (FEV1) and FEV1 z-scores a trend toward a decrease. In 2019, chronic Staphylococcus aureus colonization, inhaled antipseudomonal antibiotic use for more than 3 months, oral nutritional supplement requirements, and oxygen support need increased. CONCLUSIONS: Patients who had indications for modulator treatments but were unable to obtain them worsened even after a year of follow-up. This study emphasized the importance of using modulator treatments for patients with CF in our country, as well as in many countries worldwide.

Evaluation of children and adolescent with cystic fibrosis by pancreatic elastography.

BACKGROUND: Cystic fibrosis (CF) is an autosomal recessively inherited disease. Clinical findings vary by age of the patient, the organ systems involved, and the severity of the CFTR gene mutation. Pancreatic and liver involvement is prominent and exocrine pancreatic insufficiency is observed in the majority of patients. Point shear wave elastography (pSWE) is a non-invasive method that can quantitatively determine tissue elasticity and stiffness. In this study, the morphological evaluation of the pancreas was performed using the pSWE technique in pediatric patients diagnosed with CF. The effectiveness of this method for the early detection of pancreatic insufficiency was investigated. METHODS: Fifty-five patients with CF (24 girls, 31 boys) and 60 healthy children (29 girls, 31 boys) without any chronic diseases and who were suitable for the pSWE examination were included in the study. RESULTS: The mean value of pSWE was 1.12 ± 0.16 in the healthy group and 0.97 ± 0.16 in the patients with cystic fibrosis. There was a statistically significant difference between the two groups (P < 0.001). Significant negative correlations were found between pSWE and age (r = -0.319; P = 0.018), height (r = -0.293; P = 0.03), serum glucose (r = -0.346; P = 0.01), HbA1C (r = -0.592; P = 0.02), and duration of the disease (r = -0.806; P < 0.001). CONCLUSIONS: Investigating pancreatic elasticity and detecting pancreatic insufficiency using pSWE (a simple, inexpensive, and non-invasive method) in the early period before overt laboratory and clinical symptoms of EPI appear can contribute positively to long-term results in young patients with CF.

Serum bicarbonate level improves specificity of Berlin Sleep Questionnaire for obstructive sleep apnea.

Several questionnaires have been developed to assist the diagnostic process in obstructive sleep apnea syndrome (OSAS). Berlin Sleep Questionnaire (BSQ) represents a validated screening tool for OSAS. Totally 450 patients admitted to the Sleep Center at Dicle University Medical Faculty were included prospectively. A risk analysis was performed for presence of OSAS using the BSQ. Arterial blood gas measurements were performed including bicarbonate (HCO3) level. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of BSQ for presence of OSAS and severe OSAS were determined. In patients with arterial HCO3 >24.94 mEq/L; sensitivity, specificity, PPV and NPV, of the BSQ were 93.04, 57.1, 98.3, and 23.5%, respectively. The addition of arterial HCO3 value increased the sensitivity of the BSQ in detecting OSAS patients. Although the cost of sleep studies is high for false positives from the BSQ plus arterial HCO3 level, this cost should be compared with the loss of work efficiency and severe healthcare costs of undiagnosed cases in the future. Therefore, finding possible OSAS cases in primary care health centers is important and adding serum HCO3 value to BSQ questionnaire may contribute to this topic.

Clinical features and accompanying findings of Pseudo-Bartter Syndrome in cystic fibrosis.

BACKGROUND: Pseudo-Bartter syndrome (PBS) is a rare complication of cystic fibrosis (CF) and there are limited data in the literature about it. We aimed to compare clinical features and accompanying findings of patients with PBS in a large patient population. METHODS: The data were collected from the Cystic Fibrosis Registry of Turkey where 1170 CF patients were recorded in 2017. Clinical features, diagnostic test results, colonization status, complications, and genetic test results were compared in patients with and without PBS. RESULTS: Totally 1170 patients were recorded into the registry in 2017 and 120 (10%) of them had PBS. The mean age of diagnosis and current age of patients were significantly younger and newborn screening positivity was lower in patients with PBS (P < .001). There were no differences between the groups in terms of colonization status, mean z-scores of weight, height, BMI, and mean FEV1 percentage. Types of genetic mutations did not differ between the two groups. Accompanying complications were more frequent in patients without PBS. CONCLUSION: PBS was detected as the most common complication in the registry. It could be due to warm weather conditions of our country. It is usually seen in younger ages regardless of mutation phenotype and it could be a clue for early diagnosis of CF.

Alterations of the neutrophil-lymphocyte ratio during the period of stable and acute exacerbation of chronic obstructive pulmonary disease patients.

OBJECTIVES: We aimed to investigate the importance of neutrophil-lymphocyte ratio (NLR) in patients with chronic obstructive pulmonary disease (COPD) for identifying the severity of inflammation and recognition of acute exacerbation. METHODS: We retrospectively enrolled 100 patients with a diagnosis of COPD exacerbation who were admitted to our clinic. Complete blood count (CBC), measurement of C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were determined within 2 h of hospital admission. Three months after an acute exacerbation, these measurements were obtained from the same patients during the stable period of COPD. The control group included 80 healthy subjects. NLR was calculated from CBC. RESULTS: NLR and other inflammatory markers, such as WBC, CRP and ESR were found to be significantly elevated in exacerbated COPD compared to stable COPD and control participants. There was a significant correlation of NLR with CRP (r = 0.415, P < 0.001), WBC (r = 0.304, P = 0.002) and ESR (r = 0.275, P = 0.035). For an NLR cutoff of 3.29, sensitivity for detecting exacerbation of COPD was 80.8% and specificity was 77.7% (AUC 0.894, P = 0.001). Some patients presenting with acute exacerbation of COPD and CRP, WBC or ESR levels lower than the optimal cut-off value had high NLR values. CONCLUSIONS: Elevated NLR can be used as a marker similar to CRP, WBC and ESR, in the determination of increased inflammation in acutely exacerbated COPD. NLR could be beneficial for the early detection of potential acute exacerbations in patients with COPD who have normal levels of traditional markers.

Serum Apelin 13 Levels in Patients With Pulmonary Embolism.

INTRODUCTION AND AIM: Expression and peptide immunoreactivity of apelin messenger RNA have been described in a variety of tissues, including gastrointestinal tract, adipose tissue, brain, kidney, liver, cardiovascular system, and lungs. This study aimed to investigate the possible involvement of the endogenous apelin in the pathophysiological events that occur in patients with pulmonary embolism (PE). MATERIALS AND METHODS: In total, 53 patients with PE and 35 healthy volunteers were included the study. This cross-sectional study was conducted at a tertiary care university hospital and among patients diagnosed as having PE. The control group consisted of healthy volunteers who applied to hospital for a routine checkup examination. Serum apelin 13 levels were measured in both the groups and their results were compared. RESULTS: The median ages were 57 and 53 years, and female-male ratios were 30/23 and 20/15, in the PE and control groups, respectively. The mean serum apelin 13 levels were found to be significantly higher in the PE group (76.94 ± 10.70 ng/mL) than in the control group (50.01 ± 7.13 ng/mL; P < .001). CONCLUSION: This study demonstrated that apelin 13 levels are elevated in patients with PE. These results suggest that apelin may be a novel biomarker and a potential therapeutic target in patients with acute PE in the future.

Primary antiphospholipid syndrome associated with pneumonia: a case report of a 16-year-old male patient.

Antiphospholipid syndrome (APS) is an autoimmune disease characterised by arterial and/or venous thrombosis and/or recurrent pregnancy loss in the presence of antiphospholipid (APL) antibodies. It is evaluated as APS when it develops associated with other systemic autoimmune diseases or primary APS if there is no concomitant disorder. In this study, we present a case of a 16-year-old male patient with primary APS. The patient was admitted with presumptive diagnosis of pneumonia, but multiple pulmonary thromboembolism (PTE) was observed on computerized tomography (CT) pulmonary angiography. APL antibodies positivity and thrombocytopenia developed in our patient. The patient was evaluated as primary APS since another etiology that could explain PTE was not found. Primary APS is a rare disease in children along with adolescents, compared with APS associated with other systemic autoimmune diseases. We present here a young male patient with primary APS and PTE to contribute to the literature. The patient initially had pneumonia but later developed PTE and thrombocytopenia.

Tuberculosis congènita: presentación de un caso infrecuente / Congenital tuberculosis: presentation of a rare case

La tuberculosis congènita es una enfermedad rara, con alta tasa de mortalidad. Es considerada el resultado de la transmisión vertical de la infección desde la placenta al feto, a través de la aspiración de líquido amniótico o por vía transplacentaria a través de las venas umbilicales. El diagnóstico de la enfermedad suele ser difícil porque los signos clínicos son inespecíficos. Se presenta el caso de un lactante varón de 48 días de vida, que fue internado por pérdida de peso, fiebre, tos, hemoptisis y dificultad respiratoria durante los últimos 20 días. Había recibido antibióticos de amplio espectro durante ese lapso, sin presentar mejoría. La radiografía de tórax mostró una consolidación con una lesión cavitaria en los campos medio y superior izquierdo. Se detectó Mycobacterium tuberculosis por reacción en cadena de la polimerasa en una muestra tomada por lavado broncoalveolar y, con ese hallazgo, se diagnosticó tuberculosis congènita. Se comenzó, entonces, el tratamiento con tuberculostáticos. El paciente falleció al 13er día de tratamiento. En lactantes con pérdida de peso, fiebre, tos, hemoptisis y dificultad respiratoria, debiera considerarse la posibilidad de tuberculosis congénita.

Congenital tuberculosis is a rare disease with a high mortality rate. Congenital tuberculosis is considered the result of mother-to-child transmission from the placenta to the fetus, through the ingestion of the amniotic fluid, or via transplacental transmission through the umbilical vein. Given the non-specific clinical signs of tuberculosis, it is usually difficult to diagnose it. The case of a 48-day-old male infant hospitalized due to weight loss, fever, cough, hemoptysis, and respiratory distress for the past 20 days, is presented. In this period, he had received broad spectrum antibiotics but with no improvement. A chest x-ray showed the presence of consolidation and a cavitary lesion in the upper and middle left lung fields. Mycobacterium tuberculosis was detected by polymerase chain reaction in a bronchoalveolar lavage specimen. Congenital tuberculosis was diagnosed based on this finding; hence, a tuberculostatic regimen was started accordingly. The patient died 13 days after treatment initiation. Congenital tuberculosis should be considered in infants with weight loss, fever, cough, hemoptysis and respiratory distress.

Congenital tuberculosis: presentation of a rare case.

Congenital tuberculosis is a rare disease with a high mortality rate. Congenital tuberculosis is considered the result of mother-to-child transmission from the placenta to the fetus, through the ingestion of the amniotic fluid, or via transplacental transmission through the umbilical vein. Given the non-specific clinical signs of tuberculosis, it is usually difficult to diagnose it. The case of a 48-day-old male infant hospitalized due to weight loss, fever, cough, hemoptysis, and respiratory distress for the past 20 days, is presented. In this period, he had received broad spectrum antibiotics but with no improvement. A chest x-ray showed the presence of consolidation and a cavitary lesion in the upper and middle left lung fields. Mycobacterium tuberculosis was detected by polymerase chain reaction in a bronchoalveolar lavage specimen. Congenital tuberculosis was diagnosed based on this finding; hence, a tuberculostatic regimen was started accordingly. The patient died 13 days after treatment initiation. Congenital tuberculosis should be considered in infants with weight loss, fever, cough, hemoptysis and respiratory distress.

Alterations in platelet count and mean platelet volume as predictors of patient outcome in the respiratory intensive care unit.

INTRODUCTION: Thrombocytopenia is associated with increased mortality in intensive care unit (ICU) patients. Mean platelet volume (MPV) reflects platelet function and activation. Elevated MPV is associated with poor outcomes and increased mortality rate in diseases that are commonly encountered in the respiratory ICU. METHODS: We retrospectively enrolled 95 patients who died in the ICU (dead group), 80 patients who improved and were transferred from the ICU (survived group), and 80 healthy individuals as controls. Laboratory parameters including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), albumin, and complete blood count (CBC) were recorded within 24 h on admission and transfered from the ICU or died. White blood cell (WBC) count, hemoglobin (Hb), red cell distribution width, MPV, platelet distribution width (PDW), and platelet count (PC) were obtained from the CBC. RESULTS: Admission PC and MPV levels were not different in the survived and dead groups. But in the survived group, admission WBC, MPV and PDW levels decreased, while PC increased when compared with admission levels. In the dead group, admission MPV and PDW levels increased, while PC decreased with respect to admission levels. The admission mean PC of the dead group was 182 103, which was above the thrombocytopenia limit. The ratio of admission thrombocytopenia was 45.3% in the dead group, which was significantly higher than that of the survived group (13.8%) (P < 0.001) CONCLUSIONS: Increasing MPV and decreasing platelet count may alert intensivists to the worse course of disease in patients who had normal platelet counts at ICU admission. The development of thrombocytopenia may also be essential to assessing the outcome of ICU patients.

Relationship between hepcidin levels and periodic limb movement disorder in patients with obstructive sleep apnea syndrome.

PURPOSE: This study was aimed to assess potential correlations between periodic leg movement (PLM) index, hepcidin levels, and iron status in patients with obstructive sleep apnea syndrome (OSAS). METHODS: Forty-four newly diagnosed OSAS patients and 49 non-apneic controls were enrolled in this study. All patients underwent polysomnographic evaluation. The hepcidin, iron, ferritin, total iron binding capacity, and C-reactive protein levels were measured. RESULTS: The mean age was 47.4 ± 7.2 years (18-68) in the OSAS group and 44.9 ± 11.1 years (23-65) in the control group. There were no differences in age, gender, and smoking between OSAS patients and controls. Mean apnea-hypopnea index (AHI) was 25.1 events/h. Mean serum hepcidin levels were significantly higher in OSAS subjects (725.9 ng/ml) than in control subjects (646.0 ng/ml) (p < 0.001). Serum iron levels were significantly lower in the OSAS and PLM disorder groups than in control subjects (p < 0.001). Serum hepcidin levels were significantly correlated with AHI (r = 0.453) and PLM index (r = 0.114). Serum iron levels were significantly negatively correlated with AHI (r = -0.169) and PLM index (r = -0.180). CONCLUSIONS: In our study, the level of hepcidin was increased in patients with OSAS. Our study indicates that levels of hepcidin correlate with the AHI and PLM index severity of OSAS.

Carvacrol and pomegranate extract in treating methotrexate-induced lung oxidative injury in rats.

BACKGROUND: This study was designed to evaluate the effects of carvacrol (CRV) and pomegranate extract (PE) on methotrexate (MTX)-induced lung injury in rats. MATERIAL AND METHODS: A total of 32 male rats were subdivided into 4 groups: control (group I), MTX treated (group II), MTX+CRV treated (group III), and MTX+PE treated (group IV). A single dose of 73 mg/kg CRV was administered intraperitoneally to rats in group III on Day 1 of the investigation. To group IV, a dose of 225 mg/kg of PE was administered via orogastric gavage once daily over 7 days. A single dose of 20 mg/kg of MTX was given intraperitoneally to groups II, III, and IV on Day 2. The total duration of experiment was 8 days. Malondialdehyde (MDA), total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI) were measured from rat lung tissues and cardiac blood samples. RESULTS: Serum and lung specimen analyses demonstrated that MDA, TOS, and OSI levels were significantly greater in group II relative to controls. Conversely, the TAC level was significantly reduced in group II when compared to the control group. Pre-administering either CRV or PE was associated with decreased MDA, TOS, and OSI levels and increased TAC levels compared to rats treated with MTX alone. Histopathological examination revealed that lung injury was less severe in group III and IV relative to group II. CONCLUSIONS: MTX treatment results in rat lung oxidative damage that is partially counteracted by pretreatment with either CRV or PE.