Development of algorithm for diagnosis of cystic fibrosis in absence of sweat chloride testing in resource-limited setting.

OBJECTIVE: To develop a diagnostic algorithm for cystic fibrosis (CF) in the setting of unavailability of sweat chloride, based on clinical features and basic laboratory investigations. METHODS: In a prospective observational study, we enrolled children with recurrent/persistent pneumonia with either malabsorption or poor growth, undergoing a sweat chloride test, between January 2019 and December 2020. They were simultaneously evaluated for aquagenic wrinkling of hands, stool fat globules, sputum for bacterial culture, blood gas, and serum electrolytes. Sensitivity and specificity were calculated for parameters having a significant difference between CF and non-CF groups. Scoring systems and algorithms for the diagnosis of CF were developed. RESULTS: Of 134 children enrolled, 46 (34%) had CF. The sensitivity and specificity of various parameters to diagnose CF was: sibling death due to respiratory illness (30.43%, 96.59%), aquagenic wrinkling (76.74%, 47.67%), metabolic alkalosis (17.78%, 94.12%), hyponatremia (28.89%, 89.41%), stool fat globules (38.46%, 81.18%), and presence of Pseudomonas in sputum culture (23.68%, 98.80%). Using coefficients of significant parameters on stepwise logistic regression, the composite score for diagnosis of CF was calculated as: 3X sibling death due to respiratory illness + 1.5X hyponatremia + 1.5X metabolic alkalosis + 1.5X aquagenic wrinkling + 1X stool fat globules + 2.5X presence of Pseudomonas in sputum culture (each of the variables scores 0 or 1 for absence and presence, respectively). The cut-off of ≥2.5 had sensitivity and specificity of 81.82% and 76.83%, respectively. CONCLUSIONS: In resource-limited settings, the proposed diagnostic algorithm can be used for the diagnosis of presumptive CF with fair sensitivity and specificity.

Clinical profile and in-hospital outcomes of COVID-19 among adolescents at a tertiary care hospital in India.

Introduction: We aimed to describe the clinical profile and risk factors for severe disease in adolescents hospitalised with coronavirus disease 2019 (COVID-19). Methods: A retrospective analysis of an admitted cohort of COVID-19 patients was performed at a tertiary hospital in North India. Adolescents aged 12-18 years who were hospitalised during the first wave (March-December, 2020) and the second wave (March-June, 2021) were included. Data on the demographic details, clinical presentation, laboratory parameters, disease severity at admission, treatments received, and in-hospital outcomes were retrieved. Results: The study included 197 adolescents with a median [inter-quartile range (IQR)] age of 15 (13-17) years, of whom 117 (59.4%) were male. Among these, 170 (86.3%) were admitted during the first wave. Underlying co-morbidities were present in nine (4.6%) patients. A total of 60 (30.9%) patients were asymptomatic. In the severity grading, 148 (84.6%) had mild, 16 (9.1%) had moderate, and 11 (6.3%) had severe disease. Fever (14.9%) and cough (14.9%) were the most commonly encountered symptoms. The median (IQR) duration of hospital stay was 10 (8-13) days, and six (3.1%) patients died in the hospital. Conclusion: Adolescents admitted with COVID-19 had predominantly asymptomatic or mild disease, and the mortality rate was 3.1%.

Continuous positive airway pressure (CPAP) for acute bronchiolitis in children.

BACKGROUND: Acute bronchiolitis is one of the most frequent causes of emergency department visits and hospitalisation in children up to three years of age. There is no specific treatment for bronchiolitis except for supportive treatment, which includes ensuring adequate hydration and oxygen supplementation. Continuous positive airway pressure (CPAP) aims to widen the lungs' peripheral airways, enabling deflation of overdistended lungs in bronchiolitis. Increased airway pressure also prevents the collapse of poorly supported peripheral small airways during expiration. Observational studies report that CPAP is beneficial for children with acute bronchiolitis. This is an update of a review first published in 2015 and updated in 2019. OBJECTIVES: To assess the efficacy and safety of CPAP compared to no CPAP or sham CPAP in infants and children up to three years of age with acute bronchiolitis. SEARCH METHODS: We conducted searches of CENTRAL (2021, Issue 7), which includes the Cochrane Acute Respiratory Infections Group Specialised Register, MEDLINE (1946 to August 2021), Embase (1974 to August 2021), CINAHL (1981 to August 2021), and LILACS (1982 to August 2021) in August 2021. We also searched the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) for completed and ongoing trials on 26 October 2021. SELECTION CRITERIA: We considered randomised controlled trials (RCTs), quasi-RCTs, cross-over RCTs, and cluster-RCTs evaluating the effect of CPAP in children with acute bronchiolitis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data using a structured pro forma, analysed data, and performed meta-analyses. We used the Cochrane risk of bias tool to assess risk of bias in the included studies. We created a summary of the findings table employing GRADEpro GDT software.  MAIN RESULTS: We included three studies with a total of 122 children (62/60 in intervention/control arms) aged up to 12 months investigating nasal CPAP compared with supportive (or 'standard') therapy. We included one new trial (72 children) in the 2019 update that contributed data to the assessment of respiratory rate and the need for mechanical ventilation for this update. We did not identify any new trials for inclusion in the current update. The included studies were single-centre trials conducted in France, the UK, and India. Two studies were parallel-group RCTs, and one study was a cross-over RCT. The evidence provided by the included studies was of low certainty; we made an assessment of high risk of bias for blinding, incomplete outcome data, and selective reporting, and confidence intervals were wide. The effect of CPAP on the need for mechanical ventilation in children with acute bronchiolitis was uncertain due to risk of bias and imprecision around the effect estimate (risk difference -0.01, 95% confidence interval (CI) -0.09 to 0.08; 3 RCTs, 122 children; low certainty evidence). None of the trials measured time to recovery. Limited, low certainty evidence indicated that CPAP decreased respiratory rate (decreased respiratory rate is better) (mean difference (MD) -3.81, 95% CI -5.78 to -1.84; 2 RCTs, 91 children; low certainty evidence). Only one trial measured change in arterial oxygen saturation (increased oxygen saturation is better), and the results were imprecise (MD -1.70%, 95% CI -3.76 to 0.36; 1 RCT, 19 children; low certainty evidence). The effect of CPAP on change in arterial partial carbon dioxide pressure (pCO2) (decrease in pCO2 is better) was imprecise (MD -2.62 mmHg, 95% CI -5.29 to 0.05; 2 RCTs, 50 children; low certainty evidence). Duration of hospital stay was similar in both the CPAP and supportive care groups (MD 0.07 days, 95% CI -0.36 to 0.50; 2 RCTs, 50 children; low certainty evidence). Two studies did not report pneumothorax, but pneumothorax did not occur in one study. No studies reported occurrences of deaths. Several outcomes (change in partial oxygen pressure, hospital admission rate (from the emergency department to hospital), duration of emergency department stay, and need for intensive care unit admission) were not reported in the included studies. AUTHORS' CONCLUSIONS: The use of CPAP did not reduce the need for mechanical ventilation in children with bronchiolitis, although the evidence was of low certainty. Limited, low certainty evidence suggests that breathing improved (a decreased respiratory rate) in children with bronchiolitis who received CPAP; this finding is unchanged from the 2015 review and 2019 update. Due to the limited available evidence, the effect of CPAP in children with acute bronchiolitis is uncertain for our other outcomes. Larger, adequately powered trials are needed to evaluate the effect of CPAP for children with acute bronchiolitis.

Predictors of mortality in children with cystic fibrosis in India.

BACKGROUND: There is a lack of studies on cystic fibrosis (CF) outcomes in children from developing countries like India. Identifying risk factors for mortality may help identify the high-risk group and plan policy management of such patients. We aimed to determine the factors associated with mortality among Indian children with CF. METHODS: In this retrospective study, we extracted demography, clinical features, laboratory and outcome data from medical records of children with CF. Bivariate and multivariate analysis was performed to identify variables associated with mortality. RESULTS: We enrolled 178 children, and there were 32 (18.0%) deaths. Median (IQR) z-score for body mass index (BMI) at last follow up was -1.5 (-2.7, -0.2) and -2.5 (-4.0, -1.6), p-value 0.039, in survived and deceased group respectively. Mean (SD) of % predicted of FEV1/FVC and FEV1 25-75 at the time of diagnosis in survived versus diseased group was 94.7 (24.1) versus 81.5 (19.1), p-value 0.063 and 56.1 (38.9) versus 45.7 (29.9), p-value 0.347, respectively. Significant factors associated with mortality included history of neonatal complications; hazard ratio (HR): 8.5 (95% confidence interval [CI]: 3.0-23.9, p < 0.001), low Z-scores for BMI at the time of diagnosis; HR: 7.1 (95% CI: 2.3-22.0, p < 0.001), FEV1/FVC at the time of diagnosis; HR: 5.1 (95% CI: 1.65-15.4, p < 0.004), and FEV1 25-75; HR: 3.6 (95% CI: 1.1-11.8, p = 0.03). CONCLUSIONS: Factors associated with increased mortality risk included neonatal complications, low BMI, and lower pulmonary function test results. Low BMI and low PFT indices can be improved upon by timely treatment of respiratory infections, better nutrition, early diagnosis, and treatment. A newborn screening program may help in early diagnosis and identification of the neonatal problem of CF.

Acute gastrointestinal injury in critically ill children: Impact on clinical outcome.

AIM: To estimate acute gastrointestinal injury (AGI) in critically ill children and association of its severity with mortality. METHODS: In a prospective cohort study, critically ill children (1 month-18 years) were enrolled. Gastrointestinal symptoms over the first week of admission were classified into AGI grades 1 through 4, using a paediatric adaptation of European Society of Intensive Care Medicine AGI definitions. Performance of AGI grades in predicting 28-day mortality was evaluated. RESULTS: Of 151 children enrolled, 71 (47%, 95% confidence interval (CI): 38.9-55.3%) developed AGI, with AGI grades 1, 2, 3 and 4 in 22.5%, 15.9%, 6.6% and 2%, respectively. The 28-day mortality progressively increased with AGI grade 0 (15%), 1 (35%), 2 (50%), 3 (70%), through 4 (100%), P < 0.001. Association of AGI grades with 28-day mortality was significant even after adjustment for disease severity, age and nutritional status (odds ratio (OR) = 2.152, 95% CI: 1.455, 3.184). Among AGI grades, and paediatric logistic organ dysfunction-2 score components, cardiovascular (OR = 1.525, 95% CI: 1.142, 2.037) and haematological (OR = 1.719, 95% CI: 1.067, 2.772) components of paediatric logistic organ dysfunction-2 score and AGI grades (OR = 1.565, 95% CI: 1.001, 2.449) showed significant association with 28-day mortality. CONCLUSIONS: Nearly half of the critically ill children developed AGI. AGI grades were independently associated with increased mortality, and mortality progressively increased with AGI grade.

Anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

BACKGROUND: Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. This is an updated version of the review. OBJECTIVES: To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 09 September 2021. We searched two ongoing trial registries (Clinicaltrials.gov and the WHO trials platform). Date of latest search: 16 August 2021. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager. MAIN RESULTS: Only one study enrolling 14 participants was eligible for inclusion in the review. The double-blind study compared a daily dose of 600 mg omalizumab or placebo along with twice daily itraconazole and oral corticosteroids, with a maximum daily dose of 400 mg. Treatment lasted six months but the study was terminated prematurely and complete data were not available. We contacted the study investigator and were told that the study was terminated due to the inability to recruit participants into the study despite all reasonable attempts. One or more serious side effects were encountered in six out of nine (66.67%) and one out of five (20%) participants in omalizumab group and placebo group respectively. AUTHORS' CONCLUSIONS: There is lack of evidence for the efficacy and safety of anti-IgE (omalizumab) therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis. There is a need for large prospective randomized controlled studies of anti-IgE therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis with both clinical and laboratory outcome measures such as steroid requirement, allergic bronchopulmonary aspergillosis exacerbations and lung function.

Wall-mounted Versus Handheld Syringe Suction for Pediatric Bronchoalveolar Lavage: A Randomized Controlled Trial.

BACKGROUND: Bronchoalveolar lavage (BAL) via flexible bronchoscopy is a valuable diagnostic technique in children. The quality of BAL is directly related to the volume of the fluid recovered. Continuous wall suctioning and handheld syringe suctioning are the 2 commonly used methods, but they are rarely compared in children. We aimed to compare the above 2 suctioning techniques for BAL in the pediatric age group. METHODS: This randomized controlled study enrolled children from 1 month to 18 years of age undergoing flexible bronchoscopy and BAL. We compared continuous wall suctioning and the handheld syringe suctioning technique. The primary outcome was the percentage of BAL fluid recovery in 2 different suctioning techniques. Secondary outcomes included technical acceptable BAL and yield of various diagnostic tests in BAL. RESULTS: The study included 73 children (48 boys) with a median (interquartile range) age of 30 (8, 108) months. There were 37 children in the wall mount group and 36 children in the syringe suction group. Baseline characteristics of the groups were similar. The wall mount suction had more recovery of BAL fluid compared with the syringe method (43.6±8.4% vs. 37.8±8.5%, P=0.004). The proportion of BAL having a fluid recovery of ≥40% was also high in the wall mount suction [31 (83.8%) vs. 17 (47.2%); P=0.001]. There was no difference in diagnostic yield between the groups. CONCLUSION: Wall mount suction had better BAL fluid recovery compared with handheld syringe suction in children undergoing flexible bronchoscopy. The diagnostic yield was similar in both groups.

Entomophthoromycosis in a child: Delayed diagnosis and extensive involvement.

Entomophthoromycosis is a rare fungal infection of the skin and subcutaneous tissue occurring predominantly in tropical and subtropical regions. In children, it mostly affects the lower half of the body. With this, we report a case of Entomophthoromycosis in a 6-year-old girl who presented late with extensive involvement of the upper half of the body. She responded well to treatment with potassium iodide and itraconazole. We also reviewed cases of Entomophthoromycosis reported in children.

Diaphragmatic atrophy and dysfunction in critically ill mechanically ventilated children.

RATIONALE: The extent of diaphragmatic atrophy and dysfunction in critically ill children from developing countries is not established. OBJECTIVES: To estimate changes in ultrasound measurements of diaphragmatic thickness over the first week of mechanical ventilation. To assess magnitude and risk factors of diaphragmatic atrophy. METHODS: In an observational cohort study, children aged 1-18 years, requiring mechanical ventilation were included. Ultrasound measurements of diaphragmatic thickness at end-expiration (DTe) and end-inspiration (DTi), and diaphragmatic thickening fraction (DTF) were performed daily during the first week of admission, and pre- and post-extubation. Diaphragmatic atrophy (%) and atrophy rate (rate of decline in DTe, % per day) were calculated. MEASUREMENTS AND MAIN RESULTS: Of 55 children (74.6% boys) enrolled, 20 (36.4%) died. Of 35 children with planned extubation, 5 (14.3%) required reintubation. Baseline median (interquartile range [IQR]) DTe, DTi, and DTF were 1.27 mm (1, 1.6), 1.76 mm (1.35, 2.10), and 33.75% (26.90, 44.60), respectively. There was a significant reduction in DTe over the first week of mechanical ventilation (p < .001), median (IQR) diaphragmatic atrophy and atrophy rate of 9.91% (5.26, 17.35) and 2.01% (1.08, 3.04) per day, respectively. Diaphragmatic atrophy rate was lower in pressure targeted ventilation (n = 44; 1.79% [1.03, 2.87]) than volume targeted ventilation (n = 11; 3.10% [1.31, 5.49]), p = .038. There was no difference in diaphragmatic parameters (atrophy rate, and peri-extubation DTe and DTF) in extubation success versus failure. CONCLUSIONS: The diaphragm undergoes progressive atrophy during the first week of mechanical ventilation in critically ill children. Future studies should evaluate ventilation strategies to reduce the diaphragmatic atrophy.

Lentil aspiration leading to likely hypersensitivity pneumonitis.

RATIONALE: A variety of inhaled antigens have been implicated to cause hypersensitivity pneumonitis (HP). We observed that children force-fed with lentil-based weaning food had persistent respiratory symptoms and radiology similar to HP. OBJECTIVES: To describe the clinical features of lentil HP. METHODS: We conducted a retrospective review of records of children with lentil HP attending Pediatric Chest Clinic at a tertiary care hospital in North India from 2008-2018. We included case records with elevated immunoglobulin G (IgG) specific for lentil antigen. MEASUREMENTS AND MAIN RESULTS: Nine children (seven boys) were identified with median (IQR) age of onset of symptoms and diagnosis at 9 (6, 12) and 11 (10, 16) months, respectively. Chronic cough (100%), shortness of breath (89%), fever (78%), vomiting (56%), and wheezing (33%) were common symptoms. Fine crackles were heard in 33% of children, none had clubbing. CT scans showed nodular opacities and consolidation in 78% and 67% children, respectively. Bronchoalveolar lavage showed increased neutrophils and lymphocytes (67% and 33%, respectively). All children showed rapid remission with systemic steroids (prednisolone), starting at a median dose of 1 (1, 1.1) mg kg-1 day-1 . One child had a clinical relapse which was treated with oral steroids again. IgG specific to lentil antigens was elevated in children with lentil HP (21->200 mgA/L) compared with children with other chronic respiratory illnesses (n = 7, <2-11.4 mgA/L). CONCLUSIONS: Lentil aspiration is an important cause of HP in infants of weaning age with force-feeding practices. Further studies are needed to identify aspirated antigens which cause HP in aspiration prone children.

Continuous positive airway pressure (CPAP) for acute bronchiolitis in children.

BACKGROUND: Acute bronchiolitis is one of the most frequent causes of emergency department visits and hospitalisation in children. There is no specific treatment for bronchiolitis except for supportive treatment, which includes ensuring adequate hydration and oxygen supplementation. Continuous positive airway pressure (CPAP) aims to widen the lungs' peripheral airways, enabling deflation of overdistended lungs in bronchiolitis. Increased airway pressure also prevents the collapse of poorly supported peripheral small airways during expiration. Observational studies report that CPAP is beneficial for children with acute bronchiolitis. This is an update of a review first published in 2015. OBJECTIVES: To assess the efficacy and safety of CPAP compared to no CPAP or sham CPAP in infants and children up to three years of age with acute bronchiolitis. SEARCH METHODS: We conducted searches of CENTRAL (2017, Issue 12), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1946 to December, 2017), Embase (1974 to December 2017), CINAHL (1981 to December 2017), and LILACS (1982 to December 2017) in January 2018. SELECTION CRITERIA: We considered randomised controlled trials (RCTs), quasi-RCTs, cross-over RCTs, and cluster-RCTs evaluating the effect of CPAP in children with acute bronchiolitis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data using a structured pro forma, analysed data, and performed meta-analyses. MAIN RESULTS: We included three studies with a total of 122 children (62/60 in intervention/control arms) aged up to 12 months that investigated nasal CPAP compared with supportive (or "standard") therapy. We included one new trial (72 children) that contributed data to the assessment of respiratory rate and need for mechanical ventilation for this update. The included studies were single-centre trials conducted in France, the UK, and India. Two studies were parallel-group RCTs and one was a cross-over RCT. The evidence provided by the included studies was low quality; we assessed high risk of bias for blinding, incomplete outcome data, and selective reporting, and confidence intervals were wide.The effect of CPAP on the need for mechanical ventilation in children with acute bronchiolitis was uncertain due to imprecision around the effect estimate (3 RCTs, 122 children; risk ratio (RR) 0.69, 95% confidence interval (CI) 0.14 to 3.36; low-quality evidence). None of the trials measured time to recovery. Limited, low-quality evidence indicated that CPAP decreased respiratory rate (2 RCTs, 91 children; mean difference (MD) -3.81, 95% CI -5.78 to -1.84). Only one trial measured change in arterial oxygen saturation, and the results were imprecise (19 children; MD -1.70%, 95% CI -3.76 to 0.36). The effect of CPAP on change in arterial partial carbon dioxide pressure (pCO2) was imprecise (2 RCTs, 50 children; MD -2.62 mmHg, 95% CI -5.29 to 0.05; low-quality evidence). Duration of hospital stay was similar in both CPAP and supportive care groups (2 RCTs, 50 children; MD 0.07 days, 95% CI -0.36 to 0.50; low-quality evidence). Two studies did not report about pneumothorax, but pneumothorax did not occur in one study. No studies reported occurrences of deaths. Several outcomes (change in partial oxygen pressure, hospital admission rate (from emergency department to hospital), duration of emergency department stay, and need for intensive care unit admission) were not reported in the included studies. AUTHORS' CONCLUSIONS: Limited, low-quality evidence suggests that breathing improved (a decreased respiratory rate) in children with bronchiolitis who received CPAP; this finding is unchanged from the 2015 review. Further evidence for this outcome was provided by the inclusion of a low-quality study for the 2018 update. Due to the limited available evidence, the effect of CPAP in children with acute bronchiolitis is uncertain for other outcomes. Larger, adequately powered trials are needed to evaluate the effect of CPAP for children with acute bronchiolitis.

Anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

BACKGROUND: Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. This is an updated version of the review. OBJECTIVES: To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 29 September 2017.We searched two ongoing trial registries (Clinicaltrials.gov and the WHO trials platform). Date of latest search: 24 January 2018. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager. MAIN RESULTS: Only one study enrolling 14 participants was eligible for inclusion in the review. The double-blind study compared a daily dose of 600 mg omalizumab or placebo along with twice daily itraconazole and oral corticosteroids, with a maximum daily dose of 400 mg. Treatment lasted six months but the study was terminated prematurely and complete data were not available. We contacted the study investigator and were told that the study was terminated due to the inability to recruit participants into the study despite all reasonable attempts. One or more serious side effects were encountered in six out of nine (66.67%) and one out of five (20%) participants in omalizumab group and placebo group respectively. AUTHORS' CONCLUSIONS: There is lack of evidence for the efficacy and safety of anti-IgE (omalizumab) therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis. There is a need for large prospective randomized controlled studies of anti-IgE therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis with both clinical and laboratory outcome measures such as steroid requirement, allergic bronchopulmonary aspergillosis exacerbations and lung function.

Anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

BACKGROUND: Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. This is an updated version of the review. OBJECTIVES: To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 27 July 2015.We searched the ongoing trial registry clinicaltrials.gov for any ongoing trials. Latest search for clinicaltrials.gov: 23 October 2015. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager. MAIN RESULTS: Only one study enrolling 14 participants was eligible for inclusion in the review. The double-blind study compared a daily dose of 600 mg omalizumab or placebo along with twice daily itraconazole and oral corticosteroids, with a maximum daily dose of 400 mg. Treatment lasted six months but the study was terminated prematurely and complete data were not available. We contacted the study investigator and were told that the study was terminated due to the inability to recruit participants into the study despite all reasonable attempts. One or more serious side effects were encountered in six out of nine (66.67%) and one out of five (20%) participants in omalizumab group and placebo group respectively. AUTHORS' CONCLUSIONS: There is lack of evidence for the efficacy and safety of anti-IgE (omalizumab) therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis. There is a need for large prospective randomized controlled studies of anti-IgE therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis with both clinical and laboratory outcome measures such as steroid requirement, allergic bronchopulmonary aspergillosis exacerbations and lung function.

Surfactant therapy for bronchiolitis in critically ill infants.

BACKGROUND: Bronchiolitis is one of the most frequent causes of respiratory failure in infants; some infants will require intensive care and mechanical ventilation. There is lack of evidence regarding effective treatment for bronchiolitis other than supportive care. Abnormalities of surfactant quantity or quality (or both) have been observed in severe cases of bronchiolitis. Exogenous surfactant administration appears to favourably change the haemodynamics of the lungs and may be a potentially promising therapy for severe bronchiolitis. This is an update of a review published in Issue 9, 2012. We did not identify any new studies for inclusion, and our conclusions remain unchanged. OBJECTIVES: To evaluate the efficacy of exogenous surfactant administration (i.e. intratracheal administration of surfactant of any type (whether animal-derived or synthetic), at any dose and at any time after start of ventilation) compared to placebo, no intervention or standard care in reducing mortality and the duration of ventilation in infants and children with bronchiolitis requiring mechanical ventilation. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Studies (CENTRAL; 2015, Issue 5) which contains the Cochrane Acute Respiratory Infections Group's Specialised Register; MEDLINE (1948 to June week 3, 2015); EMBASE (1974 to June 2015); CINAHL (1982 to June 2015); LILACS (1985 to June 2015); and Web of Science (1985 to June 2015). SELECTION CRITERIA: We considered prospective, randomised controlled trials (RCTs) and quasi-RCTs evaluating the effect of exogenous surfactant in infants and children with bronchiolitis requiring mechanical ventilation. DATA COLLECTION AND ANALYSIS: Two review authors selected studies independently. We extracted the data using a predefined proforma, independently analysed the data, and performed meta-analyses. MAIN RESULTS: We included three small RCTs enrolling 79 participants. Two trials did not use a placebo in the control arms and the third trial used air placebo. Two included studies reported no mortality. We judged all three of the included studies to be at low risk or unclear risk across all risk of bias categories; we did not judge any of the studies to be at high risk of bias in any category. Our pooled analysis of the three trials revealed that duration of mechanical ventilation was not significantly different between the groups (mean difference (MD) -63.04, 95% confidence interval (CI) -130.43 to 4.35 hours) but duration of intensive care unit (ICU) stay was less in the surfactant group compared to the control group: MD -3.31, 95% CI -6.38 to -0.25 days. After excluding one trial which produced significant heterogeneity, the duration of mechanical ventilation and duration of ICU stay were significantly lower in the surfactant group compared to the control group: MD -28.99, 95% CI -40.10 to -17.87 hours; and MD -1.81, 95% CI -2.42 to -1.19 days, respectively. Use of surfactant had favourable effects on oxygenation and CO2 elimination. No adverse effects and no complications were observed in any of the three included studies. The level of evidence for duration of mechanical ventilation, duration of intensive care unit stay, oxygenation parameters, and carbon dioxide parameters was of moderate quality. AUTHORS' CONCLUSIONS: Use of surfactant had favourable effects on duration of mechanical ventilation, duration of ICU stay, oxygenation, and CO2 elimination. However, the studies are few and small (n = 79) so available evidence is insufficient to establish the effectiveness of surfactant therapy for bronchiolitis in critically ill infants who require mechanical ventilation. There is a need for larger trials with adequate power and a cost-effectiveness analysis to evaluate the effectiveness of exogenous surfactant therapy for infants with bronchiolitis who require intensive care management.

Continuous positive airway pressure (CPAP) for acute bronchiolitis in children.

BACKGROUND: Acute bronchiolitis is one of the most frequent causes of emergency department visits and hospitalisation in infants. There is no specific treatment for bronchiolitis except for supportive therapy. Continuous positive airway pressure (CPAP) is supposed to widen the peripheral airways of the lung, allowing deflation of over-distended lungs in bronchiolitis. The increase in airway pressure also prevents the collapse of poorly supported peripheral small airways during expiration. In observational studies, CPAP is found to be beneficial in acute bronchiolitis. OBJECTIVES: To assess the efficacy and safety of CPAP compared to no CPAP or sham CPAP in infants and children up to three years of age with acute bronchiolitis. SEARCH METHODS: We searched CENTRAL (2014, Issue 3), MEDLINE (1946 to April week 2, 2014), EMBASE (1974 to April 2014), CINAHL (1981 to April 2014) and LILACS (1982 to April 2014). SELECTION CRITERIA: We considered randomised controlled trials (RCTs), quasi-RCTS, cross-over RCTs and cluster-RCTs evaluating the effect of CPAP in children with acute bronchiolitis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data using a structured proforma, analysed the data and performed meta-analyses. MAIN RESULTS: We included two studies with a total of 50 participants under 12 months of age. In one study there was a high risk of bias for incomplete outcome data and selective reporting, and both studies had an unclear risk of bias for several domains including random sequence generation. The effect of CPAP on the need for mechanical ventilation in children with acute bronchiolitis was uncertain due to imprecision around the effect estimate (two RCTs, 50 participants; risk ratio (RR) 0.19, 95% CI 0.01 to 3.63; low quality evidence). Neither trial measured our other primary outcome of time to recovery. One trial found that CPAP significantly improved respiratory rate compared with no CPAP (one RCT, 19 participants; mean difference (MD) -5.70 breaths per minute, 95% CI -9.30 to -2.10), although the other study reported no difference between groups with no numerical data to pool. Change in arterial oxygen saturation was measured in only one trial and the results were imprecise (one RCT, 19 participants; MD -1.70%, 95% CI -3.76 to 0.36). The effect of CPAP on the change in partial pressure of carbon dioxide (pCO2) was also imprecise (two RCTs, 50 participants; MD -2.62 mmHg, 95% CI -5.29 to 0.05; low quality evidence). Duration of hospital stay was similar in both of the groups (two RCTs, 50 participants; MD 0.07 days, 95% CI -0.36 to 0.50; low quality evidence). Both trials reported no cases of pneumothorax and there were no deaths in either study. Change in partial pressure of oxygen (pO2), hospital admission rate (from emergency department to hospital), duration of emergency department stay, need for intensive care unit admission, local nasal effects and shock were not measured in either study. AUTHORS' CONCLUSIONS: The effect of CPAP in children with acute bronchiolitis is uncertain due to the limited evidence available. Larger trials with adequate power are needed to evaluate the effect of CPAP in children with acute bronchiolitis.

Bronchial asthma with ABPA presenting as PTE.

Allergic bronchopulmonary aspergillosis (ABPA), as a complication of asthma, is rare in children. The persistent and poorly-controlled asthma leading to cor pulmonale is not uncommon in adults but rarely described in the pediatric age group. Here, we report a case of asthma and ABPA complicated by pulmonary thrombo-embolism and cor pulmonale. To the best of our knowledge, such association has never been reported in the pediatric age group.

Anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

BACKGROUND: Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. OBJECTIVES: To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 21 January 2013.We searched the ongoing trial registry clinicaltrials.gov for any ongoing trials. Latest search for clinicaltrials.gov: 22 February 2013. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager 5.1. MAIN RESULTS: Only one trial enrolling 14 patients was eligible for inclusion in the review. The study was terminated prematurely and complete data were not available. We contacted the study investigator and were told that the study was terminated due to the inability to recruit patients into the study despite all reasonable attempts. One or more serious side effects were encountered in six out of nine (66.67%) and one out of five (20%) patients in omalizumab group and placebo group respectively. AUTHORS' CONCLUSIONS: There is lack of evidence for the efficacy and safety of anti-IgE (omalizumab) therapy in patients with cystic fibrosis and allergic bronchopulmonary aspergillosis. There is a need for large prospective randomized controlled trials of anti-IgE therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis with both clinical and laboratory outcome measures such as steroid requirement, allergic bronchopulmonary aspergillosis exacerbations and lung function.

Ketamine for management of acute exacerbations of asthma in children.

BACKGROUND: Asthma is the most common chronic disease in children, and children with asthma frequently visit the paediatric emergency departments with acute exacerbations. Some of these children fail to respond to standard therapy (aerosol beta(2)-agonist with or without aerosol anticholinergic and oral or parenteral corticosteroids) for acute asthma leading to prolonged emergency department stay, hospitalisation, morbidity (e.g. barotrauma, intubation) and death, albeit rarely. Ketamine may relieve bronchospasm and is a potentially promising therapy for children with acute asthma who fail to respond to standard treatment. OBJECTIVES: To evaluate the efficacy of ketamine compared to placebo, no intervention or standard care for management of severe acute asthma in children who had not responded to standard therapy. SEARCH METHODS: We identified trials from the Cochrane Airways Group Specialised Register of trials (CAGR) and ClinicalTrials.gov. We reviewed reference lists of all primary studies and review articles for additional references. We contacted authors of identified trials and asked them to identify other published and unpublished studies. The latest search was in July 2012. SELECTION CRITERIA: Randomised controlled trials comparing ketamine to placebo or standard care in children (up to 18 years of age) presenting with an acute asthma exacerbation who had not responded to standard therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies. The data were extracted in pre-defined proforma and were analysed independently by two review authors. The data analysis was performed using Review Manager 5.1. MAIN RESULTS: A single study enrolling 68 non-intubated children was found eligible for inclusion in review. The study had low or unclear risk of bias. It demonstrated no significant difference in respiratory rate, oxygen saturation, hospital admission rate (odds ratio (OR) 0.77; 95% confidence interval (CI) 0.23 to 2.58) and need for mechanical ventilation between ketamine (0.2 mg/kg intravenous bolus over one to two minutes, followed by a 0.5 mg/kg per hour continuous infusion for two hours) and placebo group. There were no significant side effects of ketamine in the study. There was also no difference in need for other adjuvant therapy (OR 2.19; 95% CI 0.19 to 25.40) and in Pulmonary Index Score (mean difference (MD) -0.40; 95% CI -1.21 to 0.41) between the groups. AUTHORS' CONCLUSIONS: The single study on non-intubated children with severe acute asthma did not show significant benefit and does not support the case studies and observational reports showing benefits of ketamine in both non-ventilated and ventilated children. There were no significant side effects of ketamine. We could not find any trials on ventilated children. To prove that ketamine is an effective treatment for acute asthma in children, there is need for sufficiently powered randomised trials of high methodological quality with objective outcome measures of clinical importance. Future trials should also explore different doses of ketamine and its role in children needing ventilation because of severe acute asthma.

Surfactant therapy for bronchiolitis in critically ill infants.

BACKGROUND: Bronchiolitis is one of the most frequent causes of respiratory failure in infants; some infants will require intensive care and mechanical ventilation. There is lack of evidence regarding effective treatment for bronchiolitis other than supportive care. Abnormalities of surfactant quantity or quality (or both) have been observed in severe cases of bronchiolitis. Exogenous surfactant administration appears to favourably change the haemodynamics of the lungs and may be a potentially promising therapy for severe bronchiolitis.  OBJECTIVES: To evaluate the efficacy of exogenous surfactant administration (i.e. intratracheal administration of surfactant of any type (whether animal-derived or synthetic), at any dose and at any time after start of ventilation) compared to placebo, no intervention or standard care in reducing mortality and the duration of ventilation in infants and children with bronchiolitis requiring mechanical ventilation. SEARCH METHODS: We searched CENTRAL 2012, Issue 4 which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1948 to May week 1, 2012), EMBASE (1974 to May 2012), CINAHL (1982 to May 2012), LILACS (1985 to May 2012) and Web of Science (1985 to May 2012). SELECTION CRITERIA: We considered prospective, randomised controlled trials (RCTs) and quasi-RCTs evaluating the effect of exogenous surfactant in infants and children with bronchiolitis requiring mechanical ventilation. DATA COLLECTION AND ANALYSIS: Two review authors selected studies independently. We extracted the data using a predefined proforma, independently analysed the data and performed meta-analyses. MAIN RESULTS: We included three small RCTs enrolling 79 participants. Two trials did not use a placebo in the control arms and the third trial used air placebo. Two included studies did not describe mortality. We judged some of the included studies to have an unclear risk of bias but none of the included studies had a high risk of bias. Our pooled analysis of the three trials revealed that duration of mechanical ventilation was not different between the groups (mean difference (MD) -63.04, 95% confidence interval (CI) -130.43 to 4.35 hours) but duration of intensive care unit (ICU) stay was less in the surfactant group compared to the control group: MD -3.31 (95% CI -6.38 to -0.25 days). After excluding one trial which produced significant heterogeneity, the duration of mechanical ventilation and duration of ICU stay were significantly lower in the surfactant group compared to the control group: MD -28.99 (95% CI -40.10 to -17.87 hours) and MD -1.81 (95% CI -2.42 to -1.19 days), respectively. Use of surfactant had favourable effects on oxygenation and CO(2) elimination. No adverse effects and no complications were observed in any of the three included studies. AUTHORS' CONCLUSIONS: The available evidence is insufficient to establish the effectiveness of surfactant therapy for bronchiolitis in critically ill infants who require mechanical ventilation. There is a need for larger trials with adequate power and a cost-effectiveness analysis to evaluate the effectiveness of exogenous surfactant therapy for infants with bronchiolitis who require intensive care management.