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.

Clinical characteristics of patients requiring lung transplantation referral in national cystic fibrosis registry data.

BACKGROUND: We aimed to determine the number of cystic fibrosis (CF) patients recorded in the Cystic Fibrosis Registry of Türkiye (CFRT) who were in need of lung transplantation (LT) referral and examine clinical differences between patients who were LT candidates due to rapid forced expiratory volume in one second (FEV1) decline and LT candidates without rapid FEV1 decline in the last year to identify a preventable cause in patients with such rapid FEV1 decline. METHODS: All CF patients recorded in the CFRT in 2018 were evaluated in terms of LT. Patients were divided into those with FEV1 below 50% and in need of LT due to a decrease of 20% or more in the previous year (Group 1) and those who did not have FEV1 decline of more than 20% in the previous year but had other indications for LT (Group 2). Demographic and clinical features were compared between the two groups. RESULTS: Of 1488 patients registered in CFRT, 58 had a need for LT. Twenty patients were included in Group 1 and others in Group 2. Our findings did not reveal any significant variations in treatment, chronic infection status, or complications between the two groups. The average weight z-score was significantly higher in Group 1. Positive correlations were detected between weight z-score and FEV1 in 2017 in Group 1 and between FEV1 values in 2017 and 2018 in Group 2. CONCLUSIONS: There appears to be a relationship between the nutritional status and weight z-scores of CF patients and pulmonary function, which may indirectly affect the need for lung transplantation referral.

Sleep-related Breathing Disorders in Children with Asthma: Impact on Asthma Control.

OBJECTIVE: To investigate the frequency of sleep-related breathing disorder and the relationship between asthma control and sleep-related breathing disorder in children with persistent asthma. STUDY DESIGN: Comparative cross-sectional study. PLACE AND DURATION OF STUDY: University of Health Sciences, Hamidiye Etfal Training and Research Hospital, Istanbul/Turkey, from January 2019 to June 2019. METHODOLOGY: Children aged 4-11 years with persistent asthma were included. At enrollment, socio-demographic and asthmatic characteristics were investigated, and pediatric sleep questionnaire and childhood asthma control tests were administered. RESULTS: Out of 120 patients, 75 (62.5%) were males and 45 (37%) females. According to GINA guidelines, asthma was well controlled in 23.3% children, partially controlled in 50.8% children and uncontrolled in 25.8% children. The frequency of habitual snoring was reported as 20.8% and the frequency of sleep-related breathing disorder was 29.2%. The prevalence of sleep-related breathing disorders was significantly higher in the uncontrolled asthma group (p <0.001). Significant-independent efficacy of physician-diagnosed allergic rhinitis, habitual snoring, and low asthma control test scores was observed in predicting sleep-related breathing disorders in multivariate logistic regression model (p <0.001). CONCLUSION: Uncontrolled asthma is associated with sleep-related disordered breathing. The authors suggest that allergic rhinitis, habitual snoring, and low asthma control test scores are important risk factors for sleep-related breathing disorders in children with persistent asthma. KEY WORDS: Asthma, Asthma control test, Allergic rhinitis, Habitual snoring, Pediatric sleep questionnaire, Sleep-related breathing disorder.

The success of the Cystic Fibrosis Registry of Turkey for improvement of patient care.

BACKGROUND: Cystic fibrosis (CF) registries play an essential role in improving disease outcomes of people with CF. This study aimed to evaluate the association of newly established CF registry system in Turkey on follow-up, clinical, growth, treatment, and complications of people with this disease. METHODS: Age at diagnosis, current age, sex, z-scores of weight, height and body mass index (BMI), neonatal screening results, pulmonary function tests, history of meconium ileus, medications, presence of microorganisms, and follow-up were evaluated and compared to data of people with CF represented in both 2017 and 2019 registry data. RESULTS: There were 1170 people with CF in 2017 and 1637 in 2019 CF registry. Eight hundred and fourteen people were registered in both 2017 and 2019 of whom z-scores of heights and BMI were significantly higher in 2019 (p = 0.002, p =0.039, respectively). Inhaled hypertonic saline, bronchodilator, and azithromycin usages were significantly higher in 2019 (p =0.001, p = 0.001, p = 0.003, respectively). The percent predicted of forced expiratory volume in 1 sec and forced vital capacity were similar in 2017 and 2019 (88% and 89.5%, p = 0.248 and 84.5% and 87%, p =0.332, respectively). Liver diseases and osteoporosis were significantly higher, and pseudo-Bartter syndrome (PBS) was significantly lower in 2019 (p = 0.011, p = 0.001, p = 0.001, respectively). CONCLUSIONS: The z-scores of height and BMI were higher, the use of medications that protect and improve lung functions was higher and incidence of PBS was lower in 2019. It was predicted that registry system increased the care of people with CF regarding their follow-up. The widespread use of national CF registry system across the country may be beneficial for the follow-up of people with CF.

Clinical findings of patients with cystic fibrosis according to newborn screening results.

BACKGROUND: Cystic fibrosis (CF) is a lethal recessive genetic disease caused by loss of function associated with mutations in the CF trans-membrane conductance regulator. It is highly prevalent (approximately 1 in 3,500) in Caucasians. The aim of this study was to compare demographic and clinical features, diagnostic tests, treatments, and complications of patients with CF whose newborn screening (NBS) with twice-repeated immune reactive trypsinogen testing was positive, normal, and not performed. METHODS: In this study, 359 of all 1,488 CF patients recorded in the CF Registry of Turkey in 2018, who had been born through the process of NBS, were evaluated. Demographic and clinical features were compared in patients diagnosed with positive NBS (Group 1), normal (Group 2), or without NBS (Group 3). RESULTS: In Group 1, there were 299 patients, in Group 2, there were 40 patients, and in Group 3, there were 20 patients. Among all patients, the median age at diagnosis was 0.17 years. The median age at diagnosis was higher in Groups 2 and 3 than in Group 1 (P = 0.001). Fecal elastase results were higher in Group 2 (P = 0.033). The weight z-score was lower and chronic Staphylococcus aureus infection was more common in Group 3 (P = 0.017, P = 0.004, respectively). CONCLUSIONS: Frequency of growth retardation and chronic S. aureus infection can be reduced with an early diagnosis using NBS. In the presence of clinical suspicion in patients with normal NBS, further analyses such as genetic testing should be performed, especially to prevent missing patients with severe mutations.

Patients eligible for modulator drugs: Data from cystic fibrosis registry of Turkey.

BACKGROUND: A better understanding of cystic fibrosis transmembrane conductance regulator biology has led to the development of modulator drugs such as ivacaftor, lumacaftor-ivacaftor, tezacaftor-ivacaftor, and elexacaftor-tezacaftor-ivacaftor. This cross-sectional study evaluated cystic fibrosis (CF) patients eligible for modulator drugs. METHODS: Data for age and genetic mutations from the Cystic Fibrosis Registry of Turkey collected in 2018 were used to find out the number of patients who are eligible for modulator therapy. RESULTS: Of registered 1488 CF patients, genetic analysis was done for 1351. The numbers and percentages of patients and names of the drugs, that the patients are eligible for, are as follows: 122 (9.03%) for ivacaftor, 156 (11.54%) for lumacaftor-ivacaftor, 163 (11.23%) for tezacaftor-ivacaftor, and 57 (4.21%) for elexacaftor-tezacaftor-ivacaftor. Among 1351 genotyped patients total of 313 (23.16%) patients are eligible for currently licensed modulator therapies (55 patients were shared by ivacaftor and tezacaftor-ivacaftor, 108 patients were shared by lumacaftor-ivacaftor and tezacaftor-ivacaftor, and 22 patients were shared by tezacaftor-ivacaftor and elexacaftor-tezacaftor-ivacaftor groups). CONCLUSIONS: The present study shows that approximately one-fourth of the registered CF patients in Turkey are eligible for modulator drugs. As, frequent mutations that CF patients have in Turkey are different from North American and European CF patients, developing modulator drugs effective for those mutations is necessary. Furthermore, as modulator drugs are very expensive currently, financial support of the government in developing countries like Turkey is noteworthy.

Seasonal, sex variations in vitamin d levels and their association with pulmonary function in children with asthma

Background/aim: We aimed to examine the seasonal and sex variations in vitamin D levels in children with asthma and their associations with lung function. Materials and methods: We conducted a cohort study involving children aged 7­17 years old with asthma. Vitamin D levels were obtained and pulmonary function tests (PFTs) were performed in winter months (December, January, and February) and at the end of summer (August, September, and October). Seasonal and sex variations in vitamin D levels and lung function were examined. Results: A total of 56 children (26 males, mean age: 11.93 ± 1.8) were enrolled. The mean vitamin D level in winter was 13.36 ± 6.31 ng/mL and increased to 22.89 ± 7.83 ng/mL at the end of summer. Vitamin D levels were significantly lower in the female participants (P = 0.002) in winter. There was no difference in vitamin D levels at the end of the summer between the sexes. No correlations were found between vitamin D levels and PFT parameters in winter or at the end of summer. Conclusion: There are seasonal and sex variations in vitamin D levels in children with asthma. Vitamin D levels do not correlate with lung function.

Frequency of Asthma and Atopic Diseases in Inflammatory Bowel Disease and Celiac Disease.

OBJECTIVE: To compare the frequency of asthma and allergic diseases in patients with inflammatory bowel disease and Celiac disease using international study of asthma and allergies in childhood questionnaire. STUDY DESIGN: Cross-sectional, descriptive study. PLACE AND DURATION OF STUDY: Pediatric gastroenterology outpatient clinics and pediatric pulmonology outpatient clinics, from May 2015 to August 2015. METHODOLOGY: Patients aged between 6 and 18 years with the diagnoses of celiac and inflammatory bowel disease were included in the study. After recording the socio-demographic characteristics of all patients, the International study of asthma and allergies in childhood questionnaire was applied and required information collected. RESULTS: Eighty-three patients (31 males, 52 females) diagnosed with celiac, 42 patients (24 males, 18 females) diagnosed with ulcerative colitis, and 28 patients (11 females, 17 males) diagnosed with Crohn's disease were included. No significant difference was found between the groups in terms of the frequency of wheezing, wheezing in the last year, lifelong allergic rhinitis, long-term use of nasal steroids, and history of eczema (p >0.05). The frequency of atopic dermatitis was significantly higher in the celiac disease group than the other groups. CONCLUSION: The frequencies of asthma and atopy are similar in patients with celiac disease and inflammatory bowel disease.

Vitamin D Status, Lung Function and Atopy in Children with Asthma.

OBJECTIVE: To determine the associations between serum 25-hydroxy vitamin D3 levels and pulmonary function test outcomes and atopy in children with asthma. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Pediatric pulmonology outpatient clinic and pediatric outpatient clinic, from December 2012 to March 2013. METHODOLOGY: Atotal of 71 asthmatic children and 77 healthy controls aged 7-17 years were recruited. Vitamin D status was assessed by measuring the serum 25-hydroxy vitamin D3 levels and compared between two groups. The relationship between serum vitamin D levels and pulmonary function test outcomes and serum IgE levels and inhalant panels were also examined in asthmatic patients. RESULTS: The serum levels of 25-hydroxy vitamin D3 were low in both the asthmatic and control participants (median = 11.8 and 9.8 ng/ml, respectively). Vitamin D levels were significantly low in the patients who had high IgE levels and high levels of specific IgE antibodies against inhalant allergens in asthmatic patients. No correlation was found between vitamin D levels and pulmonary function test outcomes in asthmatic patients (p>0.05). CONCLUSION: Vitamin D levels are not associated with pulmonary function test outcomes. However, low vitamin Dlevels are associated with atopy.

Asthma control test and pediatric asthma quality of life questionnaire association in children with poor asthma control.

The aim of this study was to evaluate the association between Pediatric Asthma Quality of Life Questionnaire (PAQLQ) and Asthma Control Test (ACT) in patients with poor asthma control. Children between 7-17 years of age with diagnosis of persistent asthma who are not on daily inhaler corticosteroid therapy were involved. At enrollment, sociodemographic and asthmatic characteristics were investigated and pulmonary function test (PFT), ACT and PAQLQ were administered. Patients were reevaluated following six week regular inhaler therapy and ACT, PAQLQ and PFT were performed. Out of 77 patients, 35 (45%) were female. The mean age was 11.62 ± 2.35 years. Following 6 weeks daily inhaler therapy, the scores of ACT, all the parameters of PAQLQ and all the parameters of PFT except FEV1/FVC were significantly increased (p < 0.05). There was a significant correlation between ACT and PAQLQ scores (r < 0.5, p=0.001). In conclusion, there is a correlation between ACT and PAQLQ.

Association between maternal depression and wheezing in preschool children.

The aim of this study was to assess whether maternal depression was associated with recurrent wheezing attacks in preschool children. A case-control study was conducted involving 51 preschool children who were hospitalized due to wheezing attacks and 50 age-matched healthy subjects. Sociodemographic characteristics of the children and their mothers were investigated. The Beck depression inventory was administered to the mothers. In the case group, the anthropometric measurements were determined to be significantly lower than in the control group (p < 0.05). The rate and severity of maternal depression were significantly higher (p < 0.05) in mothers of cases. Multivariate regression analysis indicated that male gender of the child and maternal history of asthma were significant risk factors for maternal depression (odds ratio 4.671; 95% CI 1.21-18.11 and 5.263, 95% CI 1.05-32.42, respectively). Having a male child with wheezing attacks and a history of maternal asthma were identified as important risk factors for maternal depression.

The evaluation of risk factors for recurrent hospitalizations resulting from wheezing attacks in preschool children.

BACKGROUND: We aimed to evaluate the risk factors in preschool children admitted to inpatient services with a diagnosis of recurrent attacks of wheezing. METHOD: The medical files of 44 preschool children with 2 or more recurrent hospitalizations resulting from wheezing between November 2011 and January 2012 were retrospectively investigated. RESULTS: There were 28 males (64 %) and 16 females. The median age was 14 months (2.0-50). The median numbers of previous wheezing attacks and hospitalizations were 4 (2-10) and 2 (2-8), respectively. Fourteen patients (32 %) had been treated for gastroesophageal reflux (GER). The previous and recent hospital evaluations were investigated. Bronchopulmonary dysplasia and anemia were significantly more common in patients with 3 or more hospitalizations for wheezing than in those with 2 hospitalizations (p = 0.010 and p < 0.001, respectively). A review of the cases with 3 or more hospitalizations revealed that a history of GER and anemia were significant risk factors. CONCLUSION: Anemia and GER are risk factors for recurrent hospitalizations resulting from wheezing and should be treated. If the history and physical examination suggest asthma, inhaler therapy treatment should be administered, with other investigations planned for patients who do not respond to treatment as expected.