To our knowledge, this is the one of the fewest pediatric studies that evaluated the serum vitamin D level in both CF and non-CF bronchiectasis patients and determined its relation to the disease outcomes.
The present study showed that the studied subjects’ mean age was 4.80±3.85 in CF patients, 9.55±4.05 in non-CF bronchiectasis, and 5.75±4.23 in controls which was ranged from 1 to 17 years.
Males were predominant in CF bronchiectasis patients (75%), while represented (50.0%) in both non-CF bronchiectasis patients and controls.
The current study showed that vitamin D deficiency and insufficiency were significantly prevalent among CF and non-CF bronchiectasis patients (95%, 85%) respectively and surprisingly among 45% of the healthy control group with the lowest vitamin D levels were among the CF patients’ group (p< 0.001) (Table 2).
Our findings could be explained by low dietary intake of vitamin D especially among the CF patients (313.80±65.66), which presented less 61% of the RDA even in the control group. Also, inadequate sun exposure was prevalent among the studied patients especially among the CF patients (85%).
Similar to our results, recent studies [28, 29] demonstrated that the prevalence of vitamin D insufficiency in the CF population is up to 90% [3]. Also, large CF centers observed that >90% of patients had vitamin D levels <30 ng/mL [30]. In addition, Brodlie and colleagues [31] found that 90% of their pediatric CF population was vitamin D insufficient, and after increasing the supplementation dose, 49% remained insufficient.
Our results also go parallel with the findings of a case control study conducted on 402 adults with non-CF bronchiectasis by Chalmers et al. [4] which showed that the median serum 25-OHD was 24.7 nmol/l and 50% of patients with bronchiectasis were vitamin D deficient and 43% insufficient, only 7% sufficient and these percentages were significantly higher in comparison with only 12% in control group.
The higher level of vitamin D deficiency in our study may be explained by poor nutritional status with lower mean BMI (P=0.062), lower socioeconomic status with bad housing among vitamin D deficient non CF bronchiectasis patients (P= 0.040) (Table S1) and the prevalence of pancreatic insufficiency (72.2%) and severe CFTR mutations (53.2%) among vitamin D-deficient CF patients (Table S2) and the absence of routine screening of vitamin D level among the studied CF patients, inadequate sun exposure and inadequate dietary intake of vitamin D among the study participants (Table 2).
The higher prevalence of vitamin D deficiency and insufficiency among the normal healthy controls (45%) compared to previous studies [32, 33] conducted on vitamin D level among the healthy subjects should raise the awareness about the importance of adequate sun exposure and routine screening of vitamin D deficiency among the Egyptian children.
Our study has found that vitamin D deficiency among CF patients was significantly linked with more frequent and mostly moderate to severe pulmonary exacerbations compared to vitamin D sufficient and insufficient groups (P=0.033, < 0.001). Similar findings were reported among vitamin D deficient non-CF bronchiectasis patients, although it was statistically non-significant (P= 0.166, 0.232) (Tables 3 and 4).
These finding may indicate a relation between vitamin D deficiency and the bronchiectasis severity as reported by several studies that frequent pulmonary exacerbations are associated with a higher risk of future exacerbations [20] and higher mortality rates [21].
Our results were also in agreement with previous retrospective studies [30, 34, 35] which have indicated that low vitamin D status in children was associated with increased number of pulmonary exacerbations of CF [36].
Similarly, McCauley et al. [34] reported that serum vitamin D level less than or equal to 20 mg/L in CF children is associated with a three times higher rate of pulmonary exacerbations than those with vitamin D levels greater than or equal to 30 mg/L(sufficient). Furthermore, having a higher serum 25-hydroxyvitamin D in children was protective of having a pulmonary exacerbation during adolescence [36].
On the same hand, Chalmers et al. [4] highlighted that vitamin D deficient non-CF bronchiectasis patients have more frequent pulmonary exacerbations and 27.4% of deficient patients had an unscheduled hospitalization for a severe exacerbation compared to 19.7% of insufficient patients and 7.1% of sufficient patients.
The previous findings may raise the possibility of the use of vitamin D therapy as a therapeutic tool for prevention and treatment of pulmonary exacerbations in bronchiectasis patients.
The current study found that a higher percentage of bacterial colonization was found among vitamin D-deficient CF group than vitamin D insufficient and sufficient groups where chronic Pseudomonas infection was significantly higher among vitamin D deficient group (80%) than the other two groups (20%, 0%) (P=0.060) (Table 5). Similar findings were found among non-CF bronchiectasis patients where 75% of chronic pseudomonas infection and 57.1% of Staphylococcus aureus colonization were more prevalent among vitamin D-deficient group (P=0.215, 0.818) (Table 6).
These findings came different with what was reported in the literature that the most commonly isolated organisms in non-CF bronchiectasis children are non-type-able Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and to a lesser extent Staphylococcus aureus and Pseudomonas aeruginosa [2]. This observation highlights the role of vitamin D deficiency in enhancing the growth of Pseudomonas aeruginosa and Staphylococcus aureus by probably influencing the innate immunity, decreasing the induction of cathelicidin [37].
Our results were consistent with the findings of Simoneau et al. [23] who found that Pseudomonas aeruginosa was a frequent pathogen in the CF patients who were vitamin D-insufficient/deficient as compared to patients with sufficient vitamin D status (29% prevalence compared with 13% prevalence in the vitamin D-sufficient group).
On the same side, Chalmers et al. [4] reported that non-CF bronchiectasis patients with vitamin D deficiency (25[OH]D less than 25 n mol/L) had more bacterial colonization and 21.4% of colonized patients had Pseudomonas aeruginosa colonization compared to 10.4% of insufficient patients and 3.6% of sufficient patients.
Our study also revealed that median (FEV1) % of predicted was significantly lower among vitamin D-deficient (66%) and insufficient (67%) non-CF bronchiectasis groups than among the sufficient group (80%) (p=0.071). The same findings were found among the CF patients, although the difference was not statistically significant (P=0.423) (Table 7)
Similar studies [2, 5, 30, 38] showed that higher vitamin D status in children and adults with CF has been associated with better lung function assessed by (FEV1).
On the same hand, Chalmers et al. [4] highlighted that vitamin-D-deficient patients had lower FEV1 % predicted (p=0.002); the median FEV1 was 68.0% (IQR 45.3–84.9%) in the vitamin D-deficient group. The study also demonstrated a more rapid decline of lung function over a 3-year follow-up period among vitamin D-deficient non-CF bronchiectasis patients.
On the contrary, previous studies [29, 39], have studied the prevalence of vitamin D deficiency in CF and examined its association with FEV1 but have found no association between vitamin D deficiency and FEV1.
Our results also showed the sensitivity of serum vitamin D for diagnosis of CF and non-CF bronchiectasis pulmonary exacerbations severity, where at a cutoff value equal or less than 22.5 ng/ml, serum vitamin D level has significantly differentiated moderate from mild pulmonary exacerbations (P= 0.004) (Fig. 1). While at a cutoff value equal or less than 16.5 ng/dl, serum vitamin D level has differentiated severe from moderate bronchiectasis pulmonary exacerbations (Fig. 2).
These findings suggest that serum vitamin D is playing an important role in determining the severity of pulmonary exacerbations which is the most contributing factor of bronchiectasis severity.