III.A. Demographical Data
A total number of 146 patients [83 (56.8%) male and 63 (43.2%) females] were enrolled in this study and divided into two groups of patients with pulmonary complications (n= 88) and without pulmonary complications (n= 58). Most patients (n=108, 74%) were born to consanguineous parents and a family history of CID was reported in 20 patients (13.7%). 108 out of 146 patients (74%) were alive, 14 patients (9.6%) were deceased, and no information was available about the survival status of 8 (5.5%) patients. The mortality rate was higher in patients with pulmonary complications compared to the other group (11.4% vs. 6.9%), although it was not statistically significant (p=0.597). The median (interquartile range (IQR)) age of disease onset was 6 (2-12) months. The median (IQR) age of diagnosis was 15 (6-48) months, and the median (IQR) age of diagnostic delay was estimated at about 6.5 (2-24) months. Patients with pulmonary complications presented the disease’s symptoms earlier compared to patients without pulmonary involvement; however, this was not significantly different (p=0.463). The detailed demographical data are provided in Table 1.
III.B. Clinical Presentations
The summary of clinical manifestations is provided in Table 2. The most common non-infectious complication among CID patients was anemia (n=101, 69.2%), which was more prevalent in patients without pulmonary complications compared to the other patients (75.9% vs. 64.8%, p=0.200).
Failure to thrive (FTT) and weight loss were the second important clinical manifestation among 40.4% and 41.1% of CID patients, respectively. Although most patients with FTT were amongst patients with pulmonary complications group, this was not statistically significant (p=0.232).
Hepatomegaly and splenomegaly were reported in 36 (24.7%) and 39 (26.7%) patients. 21 Out of 36 (58.3%) patients with hepatomegaly and 20 out of 39 (51.2%) patients with splenomegaly also suffered from pulmonary complications. Overall, hepatomegaly (25.9% vs. 23.9%) and splenomegaly (32.8% vs. 22.7%) were higher among patients without pulmonary complications compared to the other group, although not statistically significant (p=0.845 and p=0.251, respectively).
The skin lesion was another prevalent clinical manifestation reported in 58 (39.7%) patients. In the group of patients with pulmonary manifestations, 31 patients (35.2%) and in the group of patients without any respiratory complications, 27 patients (46.6%) were diagnosed with skin lesions in medical examinations. However, these findings were not significantly different between these groups (p=0.226).
Nineteen patients (13.0%) were suffered from variable autoimmune disorders with higher frequency in patients without pulmonary complications (17.2% vs. 10.2%, p=0.315), including rheumatoid arthritis/juvenile idiopathic arthritis (n=8, 42.1%), Kawasaki disease (n=5, 26.3%), systemic lupus erythematous (n=4, 21.0%), insulin dependent diabetes mellitus (n=2, 10.5%), autoimmune hemolytic anemia (n=2, 10.5%), scleroderma (n=1, 5.3%), and celiac disease (n=1, 5.3%).
III.C. Imaging and Laboratory Findings
Thoracic CT was available in 48 out of 88 patients (54.5%) with pulmonary complications. Re-evaluation of documented CTs revealed parenchymal disorders (pneumonia (n=35, 39.8%), pulmonary nodules (n=3, 3.4%), atelectasis (n=1, 1.1%), interstitial lung disease (n=1, 1.1%), Figure S1), airway disorder (bronchiectasis (n=11, 12.5%)), and pleural disorder (pneumothorax (n=1, 1.1%)). In four patients, BAL results were available and consisted of fungi (n=2), gram positive cocci (n=1), and resistant Acinetobacter (n=1).
The median number of white blood cells (WBC) in patients with pulmonary complications was slightly higher compared to patients without pulmonary manifestations (7900 μl vs. 7650 μl); however, this was not significantly different (p=0.91). In contrast, the median percentage of lymphocytes was higher in patients who did not show any respiratory manifestations, 43% (27.3%-62.9%) in comparison patients diagnosed with pulmonary complications 38% (26%-52.5%). The median number of CD4 T cells was significantly higher in patients without any respiratory manifestations (30 cell/μl) compared to patients who developed various types of respiratory symptoms (22 cell/μl) (p= 0.012). Moreover, the median number of CD8 T cells in patients with pulmonary complications was significantly higher than a group of patients without any respiratory symptoms (26.50 cell/μl vs. 19 cell/μl, p=0.005).
The median level of IgG was reported to be higher in patients with pulmonary complications (607 md/dL) compared to the group of patients without respiratory manifestation (508.5 mg/dL) (p=0.316). On the other hand, the median level of IgA (59 mg/dL vs. 55 mg/dL) and IgM (81 mg/dL vs. 75 mg/dL) was higher in the group of patients who were not diagnosed with any respiratory complications compared to patients with pulmonary symptoms (p=0.532 vs. p=0.805). More details about the laboratory findings are provided in Table 3.