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stability of imaging abnormalities when treatment was withdrawn or who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.