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.

Respiratory muscle strength, exercise capacity and physical activity in patients with primary ciliary dyskinesia: A cross-sectional study.

BACKGROUND AND OBJECTIVES: The pathophysiological mechanisms of primary ciliary dyskinesia (PCD) may affect many functions, including respiratory, physical, and health status. This study aimed to compare respiratory muscle strength, inspiratory muscle endurance, muscle strength, exercise capacity, physical activity levels, and quality of life in PCD patients and controls. METHODS: Twenty-seven patients and 28 controls were included. Respiratory muscle strength (maximal inspiratory (MIP) and maximal expiratory (MEP) pressures), inspiratory muscle endurance (incremental threshold loading test), muscle strength (quadriceps femoris, shoulder abductor, elbow flexor, handgrip), exercise capacity (6-min walk test (6MWT)), physical activity and quality of life (QOL-PCD) were evaluated. RESULTS: MIP, inspiratory muscle endurance, quadriceps femoris, and handgrip muscle strength, 6MWT distance, total energy expenditure; childrens' (6-12 years) and their parents' physical function, upper, lower respiratory, and hearing symptoms and treatment burden QOL-PCD subscales scores were significantly lower in patients compared with controls (p < 0.05). The 66.7% of patients did not meet the optimal number of steps. MEP, shoulder abductor, and elbow flexor muscle strength, active energy expenditure, physical activity duration, average metabolic equivalents, number of steps, lying time, and sleep duration; childrens' and their parents' other subscales and adolescents' all QOL-PCD subscales scores were similar between groups (p > 0.05). CONCLUSION: Inspiratory muscle strength and endurance, lower extremity and total muscle strength, exercise capacity, total energy expenditure, and childrens' quality of life are impaired compared to healthy controls. Decreased physical activity level is prevalent in these patients. Effects of pulmonary rehabilitation on these impaired outcomes for PCD patients should be investigated. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03370029; December 12, 2017.

The Genetic Analysis of Cystic Fibrosis Patients With Seven Novel Mutations in the CFTR Gene in the Central Anatolian Region of Turkey.

BACKGROUND: Cystic fibrosis, a pulmonary disease which is an autosomal recessive, inherited, multisystemic genetic disease commonly seen in the Caucasian race, is the most frequent cause of mortality and morbidity. So far, more than 2000 disease-causing gene variants have been found and this number has been increasing with the studies conducted. Although there is not yet enough data that include the Turkish population, the recent increase of studies is noteworthy. AIMS: To discover the genetic variation in patients diagnosed with cystic fibrosis in the Central Anatolian region. STUDY DESIGN: Cross-sectional study. METHODS: The study was carried out in the Central Anatolian region in 3 pediatric pulmonology departments (Kayseri, Konya, and Ankara) in Turkey between July 2014 and December 2017. The Sanger and Next Generation Sequence analyses were used for exon and exon-intron boundaries in the cystic fibrosis transmembrane conductance regulatory (CFTR) gene, and in selected patients, mutation analysis was performed using the Multiplex Ligation-dependent Probe Amplification technique for large deletions and duplications. RESULTS: CFTR gene analysis was performed for 316 patients and 215 of them were genetically diagnosed with cystic fibrosis. Sixtythree different variants were defined in these patients and 7 of these were large deletions/duplications detected with the MLPA method. The most frequent variants were F508del (29.6%), G85E (8.2%), N1303K (8.2%), Y515* (7.5%), and G542* (3.4%). CONCLUSION: Using sequencing and Multiplex Ligation-dependent Probe Amplification methods, the identification of seven new mutations that were not previously reported in the literature contributes to a better understanding of the heterogeneous nature of CFTR mutations in the Turkish population. When no mutations are detected (pathogenic/probably pathogenic) in clinically compatible cases, Multiplex Ligationdependent Probe Amplification analysis contributes significantly to the diagnosis.

Risk factors for recurrent pulmonary exacerbation in idiopathic pulmonary hemosiderosis.

OBJECTIVES: To evaluate the risk factors of recurrent pulmonary exacerbation and poor prognosis in children with idiopathic pulmonary hemosiderosis (IPH). METHODS: In this multicenter study, 54 patients with a diagnosis of IPH were included. Medical records were retrospectively reviewed from three tertiary care hospitals between 1979 and 2019. Also, current information and the long-term progress of patients was determined by contacting the families by telephone. RESULTS: A total of 54 children were included. The median age of onset of symptoms was 4.5 years (3 months to 15.8 years). The median time from onset to diagnosis was 0.9 years (0.25 months to 12 years). The mean number of recurrent episodes per child in the recurrence-positive group was 3.55 (1-15). Univariate analysis demonstrated that patients presenting with hypoxia or requiring transfusion at the time of presentation had significantly more recurrence episodes (p = .002). Multivariate analysis showed that the presence of hypoxia at the time of initial presentation was a significant independent predictor of recurrent episodes (p = .027). The median follow-up was 3.3 years (0.75 months to 27 years). There was a significant relationship between the presence of hypoxia, transfusion history, antinuclear antibody positivity, and elevated transaminases at the time of initial evaluation and treatment response. CONCLUSIONS: The present study provides substantial information regarding factors that may affect recurrent exacerbations and prognosis in children with IPH. Demonstrating hypoxia as an independent risk factor in recurrence episodes could guide physicians in the planning of treatment strategies.

Multicentric analysis of childhood tuberculosis in Turkey.

Only a few series of pediatric tuberculosis (TB) have been reported in the last 20 years. The purpose of this study was to evaluate the clinical, radiological, microbiological, and treatment characteristics of childhood TB. A total of 539 children with childhood TB diagnosed over a 12-year period (1994-2005) in 16 different centers in Turkey participated in the study. The medical records of all childhood TB patients were investigated. A total of 539 children (274 males, 265 females) with childhood TB aged 10 days-17 years participated in the study. Age distribution was nearly equal among all age groups. We detected the index case in 39.8% of the patients. More than one index case was detected in 17.3% of the patients. A minimum 15-mm induration is accepted on tuberculin skin test (TST) following Bacillus Calmette-Guérin (BCG) vaccination. The TST was positive in 55.3% of the patients. Acid-fast bacillus smear was positive in 133, and polymerase chain reaction for Mycobacterium tuberculosis was positive in 45 patients. In 75 patients (13.9%), cultures yielded M. tuberculosis. One hundred fifty-one patients (28%) did not present for followup, and families of 5 patients (0.9%) discontinued the treatment. Pulmonary TB (n=285) and meningeal TB (n=85) were the most frequent diseases. In 29% of the patients, there was poor adherence to treatment or patients were lost to follow-up. We have demonstrated that household contact screening procedures play a major and important role, especially considering the high ratio of cases with contact index cases. We also recommend that the positive TST values should be reviewed according to the local cut-off data and should be specified in as many countries as possible. In view of the considerably high percentages of patients lost to follow-up and treatment discontinuation observed in our study, we suggest that application of directly observed treatment short-course (DOTS) is preferable.

Unfinished battle with childhood tuberculosis: is it curable with less drugs and shorter duration?

INTRODUCTION: Tuberculosis is still a global health problem all over the world despite its mortality has been decreased with effective treatment regimens. Poor treatment adherence, acquired drug resistance, treatment failure and relapse are the major problems during the course of the tuberculosis treatment. Intermittent regimens have the advantages of reducing the side effects and the cost of the therapy and increasing the adherence, especially in resource-limited areas; and have been documented to be as effective as daily regimen in the paediatric population. In this study, we compared the results of 6-month and 9-month intermittent-therapy regimens with two drugs, given to the children with pulmonary and extrapulmonary tuberculosis at our hospital. MATERIALS AND METHODS: One hundred and fifteen patients with pulmonary and extrapulmonary tuberculosis other than meningitis, who had been given intermittent anti-tuberculosis therapy between 1986 and 2001, were evaluated retrospectively. Fifty one patients were given isoniazid and rifampin daily for 15 days, followed by the same drugs and doses twice weekly for a total of 9-months. Also, 64 patients were treated with the same regimen for a total of 6-months. RESULTS: Clinical recovery was observed in 75% and 79% of pulmonary tuberculosis patients at the first month of therapy in group 1 (9-month group) and group 2 (6-month group), respectively. Radiological recovery was noted between 0-6 months in 81% of the patients in group 1 and 86% of the patients in group 2. According to the clinical and radiological recovery times, no significant difference was detected between the two groups (p> 0.05). Similar results had been observed in extrapulmonary tuberculosis (p> 0.05). Follow-up periods ranged from 7 months to 15 years. There was no case of early relapse. Late relapse was noted in 4 patients, who had been received 9-month therapy (group 1). CONCLUSION: Six-month intermittent therapy with two drugs is as efficacious as 9-month intermittent-therapy in childhood pulmonary and extrapulmonary tuberculosis, other than meningitis.