Journal of Pulmonary Medicine & Respiratory Research Category: Medical Type: Research Article
Vitamin D and Pneumonia in Children: A Case Control Study
- Kana Ram Jat1*, Jasbinder Kaur2, Vishal Guglani3
- 1 Department Of Pediatrics, All India Institute Of Medical Sciences, Government Medical College And Hospital, Delhi 110029, India
- 2 Department Of Biochemistry, Government Medical College And Hospital, Chandigarh, India
- 3 Department Of Pediatrics, Government Medical College And Hospital, Chandigarh, India
*Corresponding Author:Kana Ram Jat
Department Of Pediatrics, All India Institute Of Medical Sciences, Government Medical College And Hospital, Delhi 110029, India
Received Date: Mar 03, 2016 Accepted Date: Apr 16, 2016 Published Date: May 02, 2016
To evaluate Vitamin D levels and its correlation with severity and outcome of pneumonia in children.
It is a case-control study.
The study was conducted at tertiary care centre from Northern India from June 2013 to June 2014.
Fifty children of 1 month to 12 years of age admitted with pneumonia were enrolled as cases. Fifty age and sex matched children without pneumonia were taken as controls.
Vitamin D levels were compared between the groups and were correlated with severity and outcome of pneumonia.
The median (IQR) age of cases and controls was 12 (5,39) months and 12 (5,39) months respectively. Overall, 76 (86.4%) children were Vitamin D deficient. The median (IQR) Vitamin D levels [cases 6.8 (2.0, 14.5), controls 7.3 (4.7, 14.6) ng/ml; p=0.362] and proportions of children having Vitamin D deficiency were similar between the groups. Vitamin D levels were not different among children with pneumonia, severe pneumonia, and very severe pneumonia (p=0.985). Odds ratio of children with pneumonia being Vitamin D deficient was 3.7 (95% CI: 0.930, 14.770; p-value 0.066). Vitamin D levels were not correlated with requirement of intensive care management, mechanical ventilation and duration of hospital stay.
Majority (86.4%) of children were Vitamin D deficient. Vitamin D levels were not different in cases and controls and were not related to severity and outcome of pneumonia.
The study is registered with Clinical Trials Registry of India (Reg. No: CTRI/2013/09/004021).
There are numerous risk factors for pneumonia in children e.g., malnutrition, poverty, ethnicity, incomplete vaccination, smoke exposure, and underlying diseases like bronchopulmonary dysplasia and congenital heart diseases [4,5]. Despite interventions to control some or more of these factors, pneumonia continues to be a major threat to child health. There is growing interest to identify other risk factors that may contribute to incidence and severity of pneumonia.
Vitamin D had many functions other than bone metabolism. Recently, Vitamin D is found to have anti-infective property through modulation of innate immune system [6,7]. Vitamin D enhances the expression of Vitamin D Receptors (VDR) and increases production of cathelicidin and beta-defensin-2 peptides which acts through toll-like receptors to elicit antimicrobial function against infections [8-13]. Vitamin D also regulates phagocytosis dependent and antibody-dependent macrophages which protect from respiratory infections . In Vitamin D deficiency, there is decreased expression of VDR resulting in impaired clearance of microbes and uncontrolled inflammation that leads to more lung damage with impaired oxygenation. Vitamin D levels are correlated with respiratory infections. Low Vitamin D production during winter season may be one of the reasons for increased respiratory infections during winter [15,16]. The hospitalization rate for children with acute respiratory infections was also correlated to skin pigmentation, one of factor determining Vitamin D production in human body .
Vitamin D is associated with risk and severity of pneumonia in various studies from world. Higher maternal Vitamin D levels were associated with lower risk of pneumonia in one study  but not in other study . In observational studies from Iran , Kuwait , Egypt , Ethiopia  and Jordan  children with rickets had higher risk of pneumonia compared to children without rickets. In case-control studies, mean Vitamin D levels were significantly lower in children with pneumonia compared to controls [13,24-26]. There are very limited studies from India. We could find only one study from Indapur, India in 2004, where higher Vitamin D levels were associated with lower risk of pneumonia . The study did not assess correlation between Vitamin D levels and outcome of pneumonia . The available studies had mixed results and Vitamin D levels may vary according to regions, therefore, it is worthy to conduct more studies on Vitamin D and pneumonia. If Vitamin D is found to have correlated with pneumonia in children, further studies with emphasis on appropriate method for correction of Vitamin D deficiency may be considered. Thus, this study was planned to assess difference in Vitamin D levels in children with pneumonia and without pneumonia and to correlate Vitamin D levels with severity and outcome of pneumonia.
Venous blood samples were collected from both cases and controls and were used to measure serum 25[OH]D levels by Chemiluminiscence assay. Serum 25[OH]D levels of less than 20 ng/ml (50 nmol/L), between 20-30 ng/ml (50-75 nmol/L), and levels of 30-80 ng/ml (75-200 nmol/L) were considered Vitamin D deficiency, insufficiency and sufficiency respectively [29-32].
|Parameters||Cases (n=50)||Controls (n=50)||P value|
|Age (months) median (IQR)||12 (5, 39)||12 (8, 48)||0.537|
|Month of enrolment||February||13||3||0.070|
|State of residence||Haryana||13||24||0.133|
|Number of siblings (median, IQR)||1 (1, 2)||2 (1, 3)||0.089|
|Duration of exclusive breast feeding (months); median, IQR||6 (4, 6)||6 (6, 8)||0.143|
|Number of children with clinical rickets||07||10||0.266|
|Number of children having complete immunization||46||42||0.525|
Vitamin D levels were not available for 12 patients (5 cases and 7 controls) due to inadequate sample or spilling during processing. Median (IQR) Vitamin D levels for all participants were 6.9 (2, 14.5) ng/ml with a minimum of 2.0 ng/ml to maximum of 40.9 ng/ml levels. Overall, 76 (86.4%), 8 (9.1%), and 4 (4.5%) children were Vitamin D deficient, insufficient and sufficient respectively. A total of 17 (7 cases, 10 controls) children had clinical rickets and difference between cases and controls was not statistically different (Table 1). The Vitamin D levels were not different between cases and controls (Table 2). Similarly, proportions of children having Vitamin D deficiency were similar among the groups (Table 2). Odds ratio of children with pneumonia being Vitamin D deficient and Vitamin D deficient or insufficient was 3.7 (95% confidence interval: 0.930, 14.770; p-value 0.066) and 3.3 (95% confidence interval: 0.330, 33.024; p-value 0.355) respectively. Hemoglobin levels were also similar between the groups (Table 2).
|Parameters||Cases (n=50)||Controls (n=50)||P value|
|Vitamin D levels (ng/ml); median, IQR||6.8 (2.0, 14.5)||7.3 (4.7, 14.6)||0.362|
|Hemoglobin (gm%); mean±SD||9.6±2.3||9.5±2.9||
0.827 (95% CI:-1.174, 1.463)
|Calcium (mg/dl); mean±SD||9.4±1.7||8.8±1.8||
0.106 (95% CI:-0.125, 1.295)
|Phosphate (mg/dl); mean±SD||4.7±1.1||4.6±1.1||
0.679 (95% CI:-0.349, 0.534)
|Alkaline phosphatase (IU/L); median, IQR||162 (127, 238)||204 (137, 274)||0.302|
|Vitamin D status*; n (%)||Deficient (<20 ng/ml)||42 (93.3%)||34 (79.1%)||0.150|
|Insufficient (20-30 ng/ml)||2 (4.4%)||6 (14.0%)|
|Sufficient (>30 ng/ml)||1(2.2%)||3 (6.9%)|
|Calcium levels (n=cases 49, control 47)||Normal||25 (51.0%)||32 (68.1%)||0.087|
|Hypo||18 (36.8%)||14 (29.8%)|
|Hyper||06 (12.2%)||1 (2.1%)|
|Phosphate levels (n=cases 49, control 47)||Normal||38 (77.6%)||40 (85.1%)||0.523|
|Hypo||8 (16.3%)||6 (12.8%)|
|Hyper||3 (6.1%)||1 (2.1%)|
|Alkaline phosphatase levels (n=cases 49, control 45)||Normal||28 (57.1%)||30 (66.7%)||0.615|
|normal range||16 (32.7%)||12 (26.7%)|
|Above normal range||5 (10.2%)||3 (6.7%)|
|*Vitamin D levels could not be assessed in 5 cases and 7 controls.|
Calcium, phosphate and alkaline phosphatase levels were similar between cases and controls (Table 2). The levels were categorized as normal, increased or decreased based on laboratory values provided by Nelson textbook of Pediatrics (19th Edition) and again there was no difference among groups (Table 2).
Among cases; 24 (48.0%), 16 (32%), and 10 (20%) children had pneumonia, severe pneumonia, and very severe pneumonia respectively. The median (IQR) Vitamin D levels in three category of pneumonia severity were 6.7 (2.0, 14.6), 8.6 (2.0, 11.8), 6.3 (2.0, 13.7) ng/ml respectively (p=0.985, Kruskal Wallis Test). Thus, Vitamin D levels were not different in children with increasing severity of pneumonia (Figure 1). Thirteen (26%) children among cases required intensive care management and four (8%) children required mechanical ventilation. Again, Vitamin D levels were not different in children who required intensive care management and/or mechanical ventilation compared those who did not require it.There was no mortality among enrolled participants. Finally, duration of hospital stay among cases had no relation with Vitamin D levels (Pearson Correlation -.082, p-value 0.739).
The previously reported case-control studies on Vitamin D and Lower Respiratory Tract Infection (LRTI) in children are shown in (Table 3). Karatekin et al.,  compared neonates admitted with ALRI in NICU to healthy neonates and found that Vitamin D levels were significantly lower in neonates with ALRI (9.12±8.88 v/s 16.33±13.42 ng/ml; p=0.011) and Vitamin D levels <10 ng/ml were more likely to develop ALRI (OR: 4.25; 95% CI 1.058-17.070; P=0.041). MacNally et al.,  compared children of less than 5 years of age admitted with pneumonia/bronchiolitis to patients without respiratory symptoms and found no difference in mean Vitamin D levels between two groups (81±40 v/s 83±30 nmol/L; p=0.71) but the cases requiring PICU admission had significantly lower Vitamin D levels compared to both controls and those admitted to ward. Muhe et al.,  compared children of less than 5 years of age admitted with pneumonia to those admitted without pneumonia and there was 13-fold higher incidence of rickets among children with pneumonia than controls (13•37 [95% CI 8•08-24•22], p<0•001). Oduwole et al.,  did not observe difference in Vitamin D levels in children of 2 months to 5 years of age admitted with pneumonia compared to those without pneumonia (104±59 v/s 130±107 nmol/L; p>0.05). Roth et al., [26,34] reported no difference in Vitamin D levels in children of 1 month to 2 years of age admitted for pneumonia compared to controls in the study conducted at Canada  but Vitamin D levels were significantly lower in children with pneumonia in the study conducted at Bangladesh . Wayse et al.,  from India observed significantly lower Vitamin D levels in children of 2 months to 5 years of age with severe pneumonia compared to healthy controls (22.8, 95% CI 21.0-24.7 v/s 38.4, 95% CI 34.2-43.1 nmol/l; p<0.001). There are few Randomized Controlled Trials (RCTs) evaluating the effect of Vitamin D supplementation in Lower Respiratory Tract Infection (LRTI) in children [35-38]. All except one  RCT concluded that Vitamin D supplementation was not beneficial in preventing or treating LRTI in children.
There may be several reasons for Vitamin D being similar among cases and controls in present study. First is overall high prevalence of Vitamin D deficiency among studied children; a large proportion of both case and controls were Vitamin deficient. Secondly we took admitted children without pneumonia as controls instead of healthy controls. As Vitamin D had anti-inflammatory and anti-infective properties and children with other diseases may have Vitamin D deficiency also. We did this intentionally to evaluate the role of Vitamin D in pneumonia specifically; therefore, we wanted cases and controls to be similar in almost all aspects except pneumonia. The ideal study to see association between Vitamin D and pneumonia should measure Vitamin D at birth and than at regular intervals and to follow children for development of pneumonia; but we could not do this because of lack of funding.
The strength of study is age and sex matched controls and prospective study. One limitation of study is lack of healthy controls.
The trial is registered at Clinical Trial Registry of India (CTRI) with registration No. CTRI/2013/09/004021.
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Citation:Jat KR, Kaur J, Guglani V (2016) Vitamin D and Pneumonia in Children: A Case Control Study. J Pulm Med Respir Res 2: 004.
Copyright: © 2016 Kana Ram Jat, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.