Method
All the children who were diagnosed as having IPH (regardless their clinical severity) and followed up in three tertiary care hospitals between 1979 and 2019 (Hacettepe University Medical Faculty Children’s Hospital, Gazi University Medical Faculty Children’s Hospital, Meram University Medical Faculty Children’s Hospital) and whose records were accessed included in the study. Data were collected from medical records retrospectively. Also, current information and the long-term progress of patients was determined by contacting the families by telephone. Ethics clearance was obtained from the Institute Ethics Committee. Criteria for diagnosis were based on iron deficiency anemia without any other apparent cause, respiratory symptoms (including hemoptysis, cough, and dyspnea), and pulmonary parenchymal infiltrates on chest imaging and exclusion of other diseases. Diagnosis was confirmed by the presence of hemosiderin-laden macrophages in bronchoalveolar lavage (BAL), gastric aspirate and/or in lung tissue specimens. The diagnosis, treatment, and follow-up of patients was performed according to the IPH management protocol of the units.
Clinical information was collected from medical records, including demographics, clinical features, comorbidities, personal history, environmental exposure, and pulmonary function testing (PFT). Hypoxia was defined by presence of oxygen saturation below 93%. The reviewed laboratory data included hemoglobin, leukocyte and reticulocyte counts, total immunoglobulin levels, and autoimmune markers. Skin tests and specific allergen statuses were recorded. Chest imaging, including X-ray and chest tomography, was evaluated from both reports and imaging. Detailed treatment information recorded.
Clinical recurrence was defined as new-emerging pulmonary infiltration in combination with acute clinically significant deterioration of respiratory symptoms and/or a decline in PFT plus new-onset hemoptysis and/or anemia after a symptom-free period of at least two months, which eventually necessitated a change in regular management. Non-recurrence was defined as resolution of clinical symptoms and imaging abnormalities, or clinical finding improvement with retention or stability of imaging abnormalities when treatment was withdrawn or who died after first attack. Patients without recurrence after the initial treatment and with complete resolution of findings were classified as having a good response. Patients who had a recurrence but responded well to oral steroids, or with reduced need for transfusion, or with minimal residual findings were classified as having a partial response. Patients who did not respond to steroids and required further immunosuppressant agents or died were classified as poor response.
The normality of distribution for numerical variables was checked using the Kolmogorov-Smirnov test. Descriptive statistics were expressed as mean ± standard deviation or median (min-max) according to the assumption of normal distribution. When data were not normally distributed, the Mann-Whitney U test was used to compare the differences between two independent groups for quantitative variables. The Kruskal-Wallis test was used to compare the difference between three or more than groups in non-normal quantitative variables. After the Kruskal-Wallis test, the Dunn test was used as a post hoc test. Fisher’s exact tests were used to examine the difference between groups for categorical variables. Binary logistic regression with the backward method was used to evaluate which independent variables (oxygen saturation <93, presence of hemoptysis at the beginning, age of initiation of symptoms, hepatomegaly) were statistically significant predictors of recurrent exacerbations. Odds ratios with 95% confidence intervals (CIs) were calculated for potential predictors of risk factors for recurrent exacerbations. A p<0.05 was accepted as statistically significant. Data were analyzed using the IBM SPSS statistics 23.0 software package.