Kana Ram Jat

Zinc Supplementation for One Year Among Children with Cystic Fibrosis Does Not Decrease Pulmonary Infection

BACKGROUND: Children with cystic fibrosis may have a deficiency of micronutrients, including zinc, which may affect their susceptibility to infections. There is a paucity of data on zinc supplementation among children with cystic fibrosis. We hypothesized that a pharmacologic dose of zinc administered daily for 12 months would reduce the need for antibiotics by 50%. METHODS: This double-blind randomized placebo-controlled trial was conducted among children with cystic fibrosis to assess the effect of zinc supplementation on the need for antibiotics and pulmonary function tests. The children, age 5–15 y, of either sex, received either 30-mg zinc tablets or similar looking placebo tablets daily in addition to standard care. They were followed up every month for a period of 12 months and whenever they had pulmonary exacerbations. Their serum zinc was estimated at baseline and at 12 months of enrollment. During each visit, the children underwent a pulmonary function test and sputum culture. RESULTS: Of a total of 43 children screened, 40 were enrolled, and of them, 37 completed the study. The median (interquartile range) number of days of the administration of antibiotics over 12 months of follow-up among the children receiving zinc was 42 (14–97) d. In the placebo group, it was 38 (15–70) d (P = .79). There were no significant differences in the percent-of-predicted FEV1 or change in FEV1 values at 12 months (P = .44). The number of children in whose respiratory specimens Pseudomonas was isolated was similar for the 2 groups at different time intervals. The adverse events reported were similar in the 2 groups. CONCLUSION: We did not find any significant difference in the need for antibiotics, pulmonary function tests, hospitalization, colonization with Pseudomonas, or the need for antibiotics for children with cystic fibrosis receiving zinc supplementation of 30 mg/d.

Vitamin D deficiency and lower respiratory tract infections in children: a systematic review and meta-analysis of observational studies

Studies related to vitamin D deficiency and lower respiratory tract infections (LRTI) in children have inconsistent findings. The objective of this systematic review was to assess the prevalence of vitamin D deficiency in children with LRTI, and to evaluate the correlation between vitamin D levels and the incidence and severity of LRTI. A total of 12 studies enrolling 2279 participants were included in our analysis. Children with LRTI were found to have significantly lower mean vitamin D levels as compared to controls There was likewise a correlation between vitamin D levels and incidence and severity of LRTI. Large randomised controlled trials are needed to evaluate effect of vitamin D supplementation for LRTI.

Etiology of Acute Respiratory Infections in Infants: A Prospective Birth Cohort Study

Background: There is paucity of studies on etiology of acute respiratory infections (ARI) in infants. The objective of this study is to document incidence and etiology of ARI in infants, their seasonal variability and association of clinical profile with etiology. Methods: A birth cohort was followed for the first year of life; for each episode of ARI, nasopharyngeal aspirates were collected to identify the causative respiratory virus(es) using multiplex real-time polymerase chain reaction assay. For lower respiratory tract infections blood culture, serum procalcitonin, serum antibodies to Mycoplasma and Chlamydia and urinary Streptococcus pneumoniae antigen were also assayed. Results: A total of 503 ARI episodes were documented in 310 infants for an incidence rate of 1.8 episodes per infant per year. Of these, samples were processed in 395 episodes (upper respiratory tract infection: 377; lower respiratory tract infection: 18). One or more viruses were detected in 250 (63.3%) episodes and viral coinfections in 72 (18.2%) episodes. Rhinovirus was the most common virus [105 (42%)] followed by respiratory syncytial virus [50 (20%)], parainfluenza virus [42 (16.8%)] and coronavirus [44 (17.6%)]. In lower respiratory tract infections, viral infections were detected in 12 (66.7%) episodes, bacterial infections in 17 (94.4%) episodes and mixed bacterial–viral infections in 8 (44.4%) episodes. Peak incidence of viruses was observed during February–March and September–November. There was no significant difference in symptom duration with virus types. Conclusion: In this cohort of infants, ARI incidence was 1.8 episodes per year per infant; 95% were upper respiratory tract infections. Viruses were identified in 63.3% episodes, and the most common viruses detected were rhinovirus, respiratory syncytial virus and parainfluenza virus.

Course of Illness after Viral Infection in Indian Children with Cystic Fibrosis

Abstract Objective To study the clinical impact of respiratory viral infection in children with cystic fibrosis (CF). Design Retrospective cohort study. Setting Tertiary care referral centre for CF in India. Participants/patients Children with CF attending a pediatric chest clinic. Methods Case records of the children with CF who had a pulmonary exacerbation with documented acute respiratory viral infection between October 2013 and December 2014 (Group I) and an equal number of controls (Group II) with pulmonary exacerbation in absence of acute respiratory viral infection were reviewed. Outcome measures The two groups were compared for the following outcomes over a period of 12–18 months: bacterial colonization, antibiotics usage, pulmonary exacerbations, numbers of outpatient visits, hospitalization and oxygen therapy and spirometric parameters. Results In total, 46 children [23 each with viral infection (Group I) and without viral infection (Group II)] of age 7–264 months were enrolled; baseline clinical status and pulmonary function tests were comparable. Mean (SD) follow-up duration in those who had viral infection and who had no viral infection was 15.7 (7.1) and 17.5 (5.4) months, respectively. On follow-up, children with viral infection (Group I) had adverse outcome in form of greater worsening of Shwachman clinical scores, number of pulmonary exacerbations requiring antibiotic usage [4 (2.1%)] and [2.8 (1.7%)], need for intravenous antibiotics 30.4% vs. 8.7%, hospitalization rates 31.8% vs. 4.3% and mortality 30.4% vs. 4.7%, respectively. Conclusion Acute viral infection in children with CF affected course of illness on follow-up, including frequent and severe pulmonary exacerbations requiring hospitalization, intravenous antibiotics, decline in CF scores and increased mortality over next 12–18 months.

Nebulized N-Acetylcysteine for Management of Plastic Bronchitis

BackgroundPlastic bronchitis is characterized by formation of extensive obstructive endobronchial casts and high recurrence rates.Case characteristicsTwo children (1-year-old girl, 7-year-old boy) who had recurrent episodes of respiratory distress with acute worsening. Bronchoscopy revealed membrane-like casts. Both children were managed with nebulized N-acetylcysteine in addition to management for asthma.OutcomeSymptom-free without recurrence for more than 9 months of follow-up.MessageNebulized N-acetylcysteine may be helpful in prevention of recurrence of plastic bronchitis due to asthma.

Sublingual Immunotherapy in Allergic Rhinitis: Search for a Suitable Biomarker Continues!

Allergic rhinitis (AR) in children is a common problem that has increased over past several decades and is frequently associated with asthma. It is due to dysregulation of immune system causing increase in inflammation and formation of specific IgE antibodies against several otherwise harmless environmental allergen/s. Among various allergens, house dust mite seems to be most common allergen for allergic rhinitis in children. Symptomatic treatment with antihistaminics (oral or nasal) and/or nasal corticosteroids is sufficient in majority of cases of AR in children. A subset of children with severe AR not responding to this conventional therapy may be benefitted by allergen-specific immunotherapy (AIT) by subcutaneous (SCIT) or sublingual (SLIT) route, the latter being increasingly used recently [1]. The guidelines have been developed for effective use of AIT in children [2]. The mechanism that leads immune tolerance in allergic rhinitis by SCIT/SLIT is complex and poorly understood till yet and researchers are trying to identify the exact mechanism. AIT corrects the immunological imbalance by shifting cytokine pattern from Th2 (IL-4, IL-5, IL-13) to Th1 type. Further, AIT reduces allergen specific IgE production, induces IgG4 blocking antibodies and promotes Treg cells that result in allergen tolerance. However, there is a lack of reliable biomarker that can be used for selecting the patient for AIT and monitoring the treatment response. Interleukin-33 (IL-33), a member of IL-1 family, is an important part of T helper 2 (Th2) immune response that upregulates in allergic conditions including allergic rhinitis [3]. Levels of IL-33 have been correlated with severity of allergic rhinitis [4]. The IL-13 is being explored as a potential biomarker for response and monitoring of AIT in allergic rhinitis. A study by Wang et al. [5] published in this issue adds to role of IL-33 in immunotherapy. Authors enrolled sixty children with AR for this case controlled prospective study. Thirty children out of these sixty children received house dust mite (HDM) allergen extract for SLIT and rest were in placebo group for 2 y. Authors found significant decline in IL-33 levels in serum and nasal lavage after 12 mo and 24 mo of SLIT treatment and reduced nasal IL-33 levels were associated with increased nasal IL-10 (a Treg cytokine) at 2 y of therapy. They also reported an in vitro test where IL-33 enhanced Th1 response (increased IL-4 and IL-5) and inhibited Th2 response (decreased Il-10) in peripheral blood mononuclear cells in allergic rhinitis [5]. Though, it is a part of multicenter study and results of whole study will provide more insights into SLIT in children with allergic rhinitis. ST2 is a receptor for IL-33 and in an another recent study, ST2 + CD45RO + CD4+ cells were increased in peripheral blood in adult patients of AR exposed to HDM and were significantly decreased after 1 y of SLIT therapy with HDM allergen [6]. A study by Nasr et al. showed that patients with AR had significantly higher levels of IgE and IL-33 in comparison to control group and level of IL-33 declined significantly along with clinical improvement [7]. The duration of SLIT is not well defined and it is used for 2–3 y, but data are not robust for long lasting effects (both clinical and biochemical) of SLIT after stopping the therapy. The assessment of cytokine levels after cessation of treatment on follow-up in index study would have given sustainability of SLIT for allergic rhinitis. Though SLIT is effective and not having major side-effects, the duration of SLIT is usually for 2–3 y and symptoms of ARmay be for approximately 3 mo in a year. The daily therapy for 3 y for relief of 3 mo symptoms may not be acceptable to all. Children with AR usually have allergy to more than one allergen and it would be a millionaire question whether using SLIT for one allergen might be effective for other allergy also. If so, how to decide best allergen for SLIT in polysensitized children, will be the next task. This aspect was not studied in * Kana Ram Jat drkanaram@gmail.com

Bordetella and Bronchiolitis: A Chance Association or More Than That?

Acute bronchiolitis is one of the most common causes of acute lower respiratory tract infection in young children with considerable morbidity and rarely, mortality. It is predominantly caused by viruses, most common being respiratory syncytial virus (RSV). Recently, Bordetella pertussis (B. pertussis) had been found in infants with bronchiolitis either in combination with virus/es or in isolation. The effect and implications of this association of B. pertussis and bronchiolitis is not clearly understood. Treatment option will be different if a child with bronchiolitis had B. pertussis infection. A single centre study by Gökçe et al. from Turkey in this issue reported B. pertussis in 44 (25.6%) patients out of 172 young infants (< 6 mo of age) hospitalized with acute bronchiolitis [1]. Out of 44 cases, 27 (61.4%) had co-infection with other viruses while 17 (38.6%) had B. pertussis as a sole pathogen. Among viruses, Respiratory syncytial virus (RSV) was most common, detected in 88 (51.1%) infants [1]. Authors did not report if there was no organism or multiple viruses in any of the infant. Further, the study did not report about sample size calculation. The prevalence of B. pertussis infection in acute bronchiolitis in previous studies ranged from 0-22.8% with nearly half to two-third having RSV coinfection, though age was varied (less than 4 mo to less than two years) and geography was different among these studies [2–6]. The high prevalence of pertussis in current study [1] may be explained by inclusion of young infants where many had no or only single dose of pertussis vaccine and different geography. It can be inferred from above studies that B. pertussis infection was more in young infants with bronchiolitis, especially below 4 mo, when there was no or incomplete pertussis vaccination. The fact was substantiated by index study where B. Pertussis positivity was more common among younger infants and in those who received either one or no dose of B. pertussis vaccine compared to those who received 2 doses of vaccine [1]. A study by Nuolivitra et al. also observed similar trend [2]. Though, culture is standard method to diagnosis B. pertussis infection, now real time polymerase chain reaction (PCR) in nasopharyngeal aspirate is frequently being used for diagnosis. But, limited availability of real time PCR in developing countries, make it difficult to diagnose B. pertussis infection in bronchiolitis. In the index study, the clinical features including severity of bronchiolitis, duration of hospitalization and laboratory parameters were not different in infants with positive and negative B. pertussis [1]. Korppi et al. also found no clinical difference between pertussis positive and negative cases [5]. A study by Nuolivirta et al. also reported similar clinical features in infants with bronchiolitis having B. pertussis positive or negative except for cough spells that were more with B. pertussis infection [2]. Piedra et al. found higher leucocyte count and prolonged hospitalization in children with bronchiolitis who were positive for pertussis [3]. A study from Paris reported paroxysmal cough and post-tussive vomiting more in infants with bronchiolitis who had RSV-pertussis co-infection [4]. Raya et al. had an interesting observation that severity of bronchiolitis was less, both at admission and during hospitalization in children with B. pertussis infection compared to those without B. pertussis infection [6]. Nicolai et al. compared clinical features in infants admitted, not necessarily bronchiolitis, with either B. pertussis or RSV infection and found that infants with pertussis had more whooping cough, apnea, cyanosis, absolute lymphocyte count, and eosinophil count, but less fever and less chest auscultation findings [7]. The current study did not describe the treatment received, especially if there was use of macrolides for any of the infant. * Kana Ram Jat drkanaram@gmail.com

Vitamin D and asthma in children: A systematic review and meta-analysis of observational studies

There is growing literature suggesting a link between Vitamin D deficiency and asthma in children, but systematic reviews are lacking. The aim of this study is to evaluate the prevalence of Vitamin D deficiency in asthmatic children and to assess the correlations of Vitamin D levels with asthma incidence, asthma control, and lung functions. PubMed, EMBASE, and Cochrane Library were searched for observational studies on asthma and Vitamin D. Two authors independently extracted data. Meta-analysis was performed using the Review Manager Software. A total of 23 (11 case–control, 5 cohort, and 7 cross-sectional) studies enrolling 13,160 participants were included in the review. Overall, Vitamin D deficiency and insufficiency were prevalent in 28.5% and 26.7% children with asthma, respectively. The mean 25-hydroxyvitamin D (25(OH)D) levels (10 studies) were significantly lower in asthmatic children as compared to nonasthmatic children with a mean difference of −9.41 (95% confidence interval [CI] −16.57, −2.25). The odds ratio of Vitamin D deficiency (eight case–control studies) was significantly higher among asthmatic children as compared to nonasthmatic children (odds ratio 3.41; 95% CI 2.04, 5.69). Correlations between Vitamin D levels and incidence of asthma, lung functions, and control of asthma had mixed results. To conclude, asthmatic children had lower 25(OH)D levels as compared to nonasthmatic children, but the correlations between 25(OH)D and asthma incidence, asthma control, and lung functions were varied. Well-designed randomized controlled trials are required to determine if children with asthma can benefit from Vitamin D supplementation.

Is it Useful to Look into Airways in Non-Resolving Pneumonia?

Non-resolving or persistent pneumonia is an important cause of morbidity and rarely, mortality in children. In developing countries like India, many of these children get empirical antitubercular therapy that imposes a threat of drug resistance. The underlying causes of non-resolving pneumonia are varied and multiple. It is important to identify a cause for proper management. The approach to identify underlying illness in nonresolving pneumonia consist of thorough history, physical examination, imaging including CT scan of chest and contrast studies, work-up for aspiration syndromes; immune deficiency illnesses, cystic fibrosis and ciliary dyskinesia and bronchoscopy. Flexible bronchoscopy (FB) is very important tool in evaluation of non-resolving pneumonia. Apart from providing anatomical details of airways, it also provides bronchoalveolar lavage (BAL), endobronchial mucosal and transbronchial lung biopsies. Bronchoalveolar lavage (BAL) is considered as a liquid biopsy of lung. A study by Bhat et al. in this issue of the Journal evaluated utility of flexible bronchoscopy in 52 children with nonresolving pneumonia [1]. Bronchoscopy revealed obvious diagnosis in 16 (30.7%) patients; bronchomalacia (7; 13.5%), neglected foreign body (5; 9.6%), hydatid cyst (2; 3.8%), and aspiration (2; 3.8%) as assessed by FEES (Functional Endoscopic Evaluation of Swallowing). Micro-organisms were detected in 22 (52.3%) patients out of 42 where BAL was performed including positive GeneXpert in two and fungus (zygomycetes) in one. Five children had foamy macrophages in BAL fluid. Though authors did not report clinical diagnosis and imaging findings, bronchoscopy definitely contributed to diagnosis in about 2/3rd cases of persistent pneumonia [1]. This study highlights that FB is an important investigation for evaluation of non-resolving pneumonia. It gives information on underlying illness and helps in management of these children. The etiology of persistent pneumonia varies, depending on the definition used and extent of work-up done. The study by Lodha et al. identified etiology in 16 (84.2%) out of 19 children with persistent pneumonia (children with tuberculosis, cystic fibrosis, and congenital heart disease were excluded from the study) and common causes included post-tubercular bronchiectasis (6; 31.6%), asthma (5; 26.3%), and recurrent aspirations (2; 10.5%) [2]. Another study from India evaluated etiology in 41 children with persistent pneumonia and found gram negative bacterial infections (12; 29.3%), aspiration syndromes (12; 29.3%), tuberculosis (8; 19.5%), HIV infection (3; 7.3%), lung malformation (2; 4.9%) and heart disease (2; 4.9%) as underlying causes [3]. In both of the studies bronchoscopy and BAL contributed in identifying the etiology. Obtaining appropriate samples from airways is always a challenge in children with respiratory illnesses. Bronchoscopy helps in obtaining samples from lower airways and subjecting BAL for advanced molecular and serological tests which help in improving the diagnostic yield of infections due to viruses, pneumocystis jiroveci, mycobacterium tuberculosis and fungal agents. Special staining like Oil red O (for diagnosis of aspiration pneumonia), Periodic acid Schiff staining (pulmonary alveolar proteinosis), iron stain for hemosiderin laden macrophages (pulmonary hemorrhage), Gomori-Grocott stain, and CD1a positive cells (more than 5% is diagnostic of pulmonary Langerhans cell histiocytosis) can be used for diagnosis. Emerging investigations like ratio of CD4/CD8 (normal ratio 1.8:1) positive cells in BAL may be helpful; decreased ratio suggests hypersensitivity pneumonitis whereas increased ratio (3.5:1 or more) is suggestive of sarcoidosis [4]. In future, * Kana Ram Jat drkanaram@gmail.com

Awareness about childhood asthma

Asthma is increasing worldwide secondary to both increasing access to healthcare with more and more asthma recognition and to urbanization. Asthma in children is different from adult with multiple phenotypes and variable natural course. It is frequently underdiagnosed and undertreated that result in poor quality of life in children and their parents. Asthma in children has significant socio-economic impact on the families because of direct treatment cost and indirect cost due to missed school days, hospitalization and lost days in parent’s job1.