MATERIALS AND METHODS
The patients, who met the CF diagnostic criteria, followed up at the Department of Pediatric Respiratory and Allergy Department, Dokuz Eylül University (DEU) Hospital, between June 2019 and July 2020 were identified.11 Patients aged between 6 and 18 years, who attended to control examinations at least 4 times a year, diagnosed with CF, and underwent a skin prick test (SPT) were included in the study.
The above skin prick test (SPT) included pollens (Grasses, Artemisia vulgaris, Alnus glutinosa, Populus alba, Betula, Fagus silvatica, Parietaria officinalis, Olea europaea); house dust mites (Dermatophagoides pteronysinus, Dermatophagoides farinae); animal epithelium (Felis domesticus, Canis familiaris, Blatella germanica); fungi (Alternaria alternata, Cladosporium herbarum, Aspergillus fumigatus) commercial extracts Alk-Abello®, Hørsholm, Denmark) . An induration diameter of 3 mm or above was considered positive for the purposes of SPT.
The demographic characteristics, CFTR gene mutations, medications in use, Total IgE, and blood eosinophil levels were retrieved from the file records of the patients. An eosinophil level of ≥470/uL were considered eosinophilia, where Total IgE of ≥77.7 IU/ml were considered high.12,13
The modified Shwachman-Kulczycki (MSK) score was used to rate the general activity, physical examination, nutritional status, and radiological findings of the patients based on a 0-25 point scale for each of the subdomains.14,15 Accordingly, the patients were classified as excellent (86-100), good (71-85), average (56-70), poor (41-55) and severe (<40) based on the disease severity group. The patients were divided into 2 groups, including those with a MSK score of >70 and those with a MSK score of ≤70, which were simultaneously rated with SPT.
The spirometry analysis results of the patients, including the forced expiratory volume in 1 second (FEV1) predicted values, forced vital capacity (FVC) values, and FEV1/FVC ratio during their latest presentation were recorded. Spirometry reference values were based on NHANES III, Hankinson et al., and Wang et al.16,17
Phlegm cultures collected from the patients were examined. Chronic infection was investigated for Pseudomonas aeruginosa (Pa),Staphylococcus aureus (Sa), Burkholderia cepacia complex(Bcc), Atypical mycobacteria (Amb), Aspergillus fumigatus (AF),Stenotrophomonas maltophilia (Sm), Escherichia coli (Ec),Haemophilus influenzae (Hi) and Klebsiella pneumoniae (Kp) microorganisms. In cases where the same microorganism was detected in 2 or more samples in at least 4 samplings during the last year, this was considered a chronic infection of the microorganism.18
Patients were divided into classes based on the estimated mutation effect on CFTR function.19 The ’minimal’ function was defined as only the existence of class I, II or III mutations, while the ’Residual’ function was defined as the existence of at least one mutation from Class IV or V. In case of at least 1 unknown mutation in the patients, these were classified as unclassified genotypes.
Allergic Bronchopulmonary Aspergillosis (ABPA) diagnosis was made pursuant to the Agarwall et al. criteria.20
Allergic rhinitis (AR) was clinically diagnosed based on the presence of symptoms, including rhinorrhea, nasal congestion, nasal itching, and sneezing pursuant to the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines.21
The patients were classified in accordance with their body mass index (BMI) during their most recent presentation as severely underweight (BMI)<16.5), underweight (BMI<18.5), normal weight (BMI=18.5–24.9,) overweight (BMI≥25), and obese (BMI≥30).22 Patients were divided into 2 groups including patients with a BMI of <18.5 and with a BMI of ≥18.5 according to their respective BMI.
Ethics Committee
The required ethics committee approval for this study was obtained from the Local Ethics Committee of Dokuz Eylül University, School of Medicine (Approval number: 2020/21-28).
Statistical Analyses
The normality hypothesis was tested by Kolmogorov Smirnov test to decide the statistical methods to be used. The non-parametric test methods were used in case any of the groups did not meet the assumption of normality. Accordingly, the Mann-Whitney U test or Student’s t-test was used in comparison of the variables obtained upon measurement in two independent groups, where the Chi-squared and Fisher exact tests were used in the analysis of the relationships between categorical variables or differences intergroup between. Pearson Correlation Test analysis was used to investigate the possible relationship between MSK scores, FEV1 predictive value and age, Total IgE level, Absolute eosinophil count (AEC), and BMI. Statistical analyses of the study were conducted using the IBM Statistical Package for the Social Sciences (SPSS) for Windows, Version 25 and a p value of ≤ 0.05 was considered statistically significant.