Methods: Lymphocyte subset enumeration test and whole exome sequencing were performed.
Results: We identified a compound heterozygous CR2 mutation (c.1916G>A and c.2012G>A) in both patients. These variants were then confirmed using Sanger sequencing.
Conclusion: Whole exome sequencing analysis of the monozygotic twins revealed compound heterozygous missense mutations in CR2.
CONTENT: We performed a systematic review and meta-analysis of the effectiveness of home environmental interventions for preventing respiratory tract infections. Ten electronic databases were searched to identify randomized controlled trials published from inception to July 31, 2020. Random-effects meta-analyses were used to assess the study outcomes. Our search identified 14 eligible studies across 12 countries, which comprised 87,428 households in total. The type of interventions on home environment included kitchen appliance and design, water supply and sanitation, house insulation, and home heating. Meta-analysis indicated a potential benefit of home environmental interventions in preventing overall respiratory tract infections (Absolute RR=0.89, 95% CI=0.78-1.01, p=0.07; Pooled adjusted RR=0.72, 95% CI=0.63-0.84, p<0.0001). Subgroup analyses depicted that home environmental interventions had no significant impact on lower respiratory tract infections, pneumonia, and severe pneumonia. A protective effect against respiratory infections was observed in high income country setting (RR=0.82, 95% CI=0.78-0.87, p<0.00001).
SUMMARY AND OUTLOOK: Home environmental interventions have the potential to reduce morbidity of respiratory tract infections. The lack of significant impact from stand-alone housing interventions suggests that multicomponent interventions should be implemented in tandem with high-quality health systems.
METHODS: A retrospective cohort analysis of patients aged ≥12 years, diagnosed with an ALRTI in primary care in 2014-15 was conducted using data from the Clinical Practice Research Datalink. Current asthma status, asthma medication and oral antibiotic use within 3 days of ALRTI infection was determined. Treatment frequency was calculated by asthma status. Mixed-effect regression models were used to explore between-practice variation and treatment determinants.
RESULTS: There were 127,976 ALRTIs reported among 110,418 patients during the study period, of whom 17,952 (16%) had asthma. Respectively, 81 and 79% of patients with and without asthma received antibiotics, and 41 and 15% asthma medication. There were significant differences in between-practice prescribing for all treatments, with greatest differences seen for oral steroids (odds ratio (OR) 18; 95% CI 7-82 and OR = 94; 33-363, with and without asthma) and asthma medication only (OR 7; 4-18 and OR = 17; 10-33, with and without asthma). Independent predictors of antibiotic prescribing among patients with asthma included fewer previous ALRTI presentations (≥2 vs. 0 previous ALRTI: OR = 0.25; 0.16-0.39), higher practice (OR = 1.47; 1.35-1.60 per SD) and prior antibiotic prescribing (3+ vs. 1 prescriptions OR = 1.28; 1.04-1.57) and concurrent asthma medication (OR = 1.44; 1.32-1.57). Independent predictors of asthma medication in patients without asthma included higher prior asthma medication prescribing (≥7 vs. 0 prescriptions OR = 2.31; 1.83-2.91) and concurrent antibiotic prescribing (OR = 3.59; 3.22-4.01).
CONCLUSION: Findings from the study indicate that antibiotics are over-used for ALRTI, irrespective of asthma status, and asthma medication is over-used in patients without asthma, with between-practice variation suggesting considerable clinical uncertainty. Further research is urgently needed to clarify the role of these medications for ALRTI.
OBJECTIVE: This systematic review aims to gather and appraise existing evidence on the associations between serum vitamin D concentrations during pregnancy and at birth and the development of eczema, wheezing, and RTIs in infants.
DATA SOURCES: PubMed, MEDLINE, ProQuest, Scopus, CINAHL, Cochrane Library and Academic Search Premier databases were searched systematically using specified search terms and keywords.
STUDY SELECTION: Articles on the associations between serum vitamin D concentrations during pregnancy and at birth and eczema, wheezing, and RTIs among infants (1-year-old and younger) published up to 31 March 2019 were identified, screened and retrieved.
RESULTS: From the initial 2678 articles screened, ten met the inclusion criteria and were included in the final analysis. There were mixed and conflicting results with regards to the relationship between maternal and cord blood vitamin D concentrations and the three health outcomes-eczema, wheezing and RTIs-in infants.
CONCLUSION: Current findings revealed no robust and consistent associations between vitamin D status in early life and the risk of developing eczema, wheezing and RTIs in infants. PROSPERO registration no. CRD42018093039.
METHOD: Air interface biofilm was cultured onto Snapwell inserts incorporated into a modified pharmacopeia deposition apparatus, the Anderson Cascade Impactor (ACI). Three different formulations including mannitol only, ciprofloxacin only and combined ciprofloxacin and mannitol were nebulised onto the P. aeruginosa biofilm using the modified ACI. Antibacterial effectiveness was evaluated using colony-forming units counts, biofilm penetration and scanning electron microscopy.
RESULTS: Nebulised mannitol promotes the dispersion of bacteria from the biofilm and demonstrated a synergistic enhancement of the antibacterial efficacy of ciprofloxacin compared to delivery of antibiotic alone.
CONCLUSIONS: The combination of ciprofloxacin and mannitol may provide an important new strategy to improve antibiotic therapy for the treatment of chronic lung infections. Furthermore, the development of a representative lung model of bacterial biofilm could potentially be used as a platform for future new antimicrobial pre-clinical screening.
METHODOLOGY: This prospective cohort study involved children 1 month to 5-years-old admitted with an LRTI. Children with asthma were excluded. Patients were reviewed at 1-, 6-, and 12-months post-hospital discharge. The parent cough-specific quality of life, the depression, anxiety, and stress scale questionnaire and cough diary for 1 month, were administered. Outcomes reviewed were number of unscheduled healthcare visits, respiratory symptoms and final respiratory diagnosis at 6 and/or 12 month-review by pediatric pulmonologists.
RESULTS: Three hundred patients with a mean ± SD age of 14 ± 15 months old were recruited. After 1 month, 239 (79.7%) returned: 28.5% (n = 68/239) had sought medical advice and 18% (n = 43/239) had cough at clinic review. Children who received antibiotics in hospital had significantly lower total cough scores (P = .005) as per the cough diary. After 1 year, 26% (n = 78/300) had a respiratory problem, predominantly preschool wheezing phenotype (n = 64/78, 82.1%). Three children had bronchiectasis or bronchiolitis obliterans. The parent cough-specific quality of life (PCQOL) was significantly lower in children with respiratory sequelae (P
METHODS: Between 2015 and 2018, we evaluated 131 out of 180 (72.8%) children of adolescents from the original studies at a single follow-up visit. We administered standardized questionnaires, reviewed medical records, undertook clinical examinations, performed spirometry, and scored available chest computed tomography scans.
RESULTS: Participants were seen at a mean age of 12.3 years (standard deviation: 2.6) and a median of 9.0 years (range: 5.0-13.0) after their original recruitment. With increasing age, rates of acute lower respiratory infections (ALRI) declined, while lung function was mostly within population norms (median forced expiry volume in one-second = 90% predicted, interquartile range [IQR]: 81-105; forced vital capacity [FVC] = 98% predicted, IQR: 85-114). However, 43 out of 111 (38.7%) reported chronic cough episodes. Their overall global rating judged by symptoms, including ALRI frequency, examination findings, and spirometry was well (20.3%), stable (43.9%), or improved (35.8%). Multivariable regression identified household tobacco exposure and age at first ALRI-episode as independent risk factors associated with lower FVC% predicted values.
CONCLUSION: Under our clinical care, the respiratory outcomes in late childhood or early adolescence are encouraging for these patient populations at high-risk of premature mortality. Prospective studies to further inform management throughout the life course into adulthood are now needed.