Extracorporeal and advanced therapies for progressive refractory near‐fatal acute severe asthma in children

Asthma is the most common chronic illness and is one of the most common medical emergencies in children. Progressive refractory near‐fatal asthma requiring intubation and mechanical ventilation can lead to death. Extracorporeal membrane oxygenation (ECMO) can provide adequate gas exchange during acute respiratory failure although data on outcomes in children requiring ECMO support for status asthmaticus is sparse with one study reporting survival rates of nearly 85% with asthma being one of the best outcome subsets for patients with refractory respiratory failure requiring ECMO support. We describe the current literature on the use of ECMO and other advanced extracorporeal therapies available for children with acute severe asthma. We also review other advanced invasive and noninvasive therapies in acute severe asthma both before and while on ECMO support.     

Association of interleukin‐13 C‐1112T and G+2044A polymorphisms with asthma: A meta‐analysis

Background and objective: Polymorphisms in the IL13 gene have been reported to be associated with susceptibility to asthma. However, a number of studies have shown inconsistent results. A meta‐analysis was performed to investigate whether polymorphisms in the IL13 gene were associated with the risk of asthma. Methods: Searches were performed of the Medline and Chinese National Knowledge Infrastructure (CNKI) databases, covering all papers published up to 31 August 2010. A recently proposed logistic regression‐based method for meta‐analysis of case–control genetic association studies was used to analyse pooled data. All statistical analyses were performed using stata version 10.0 software. Results: The IL13 C‐1112T and G+2044A polymorphisms were investigated in 10 and 14 studies, respectively. The summary estimates suggested that both these polymorphisms were associated with susceptibility to asthma. Carriers of the IL13 ?1112T allele had a 38.9% increased risk of asthma compared with homozygotes (?1112CC) (odds ratio (OR) 1.389, 95% confidence interval (CI): 1.103–1.749). Carriers of the IL13+2044A allele had a 40.0% increased risk of asthma compared with homozygotes (+2044GG) (OR 1.400, 95% CI: 1.137–1.724). In a subgroup analysis by ethnicity, the IL13 ?1112T allele was associated with an increased risk of asthma among Caucasians (OR 1.629, 95% CI: 1.255–2.113) but not among Asians, and the IL13+2044A allele was associated with an increased risk of asthma among Asians (OR 1.436, 95% CI: 1.101–1.873) but not among Caucasians. Conclusions: This meta‐analysis indicated that the IL13 C‐1112T and G+2044A polymorphisms predispose to asthma. Further studies, including pooling of individual data to facilitate evaluation of gene–gene and gene–environment interactions between these IL13 gene polymorphisms and asthma susceptibility, are recommended.     

Childhood measles contributes to post‐bronchodilator airflow obstruction in middle‐aged adults: A cohort study

Background and objective

Chronic obstructive pulmonary disease (COPD) has potential origins in childhood but an association between childhood measles and post‐bronchodilator (BD) airflow obstruction (AO) has not yet been shown. We investigated whether childhood measles contributed to post‐BD AO through interactions with asthma and/or smoking in a non‐immunized middle‐aged population.

Methods

The population‐based Tasmanian Longitudinal Health Study (TAHS) cohort born in 1961 (n = 8583) underwent spirometry in 1968 before immunization was introduced. A history of childhood measles infection was obtained from school medical records. During the fifth decade follow‐up (n = 5729 responses), a subgroup underwent further lung function measurements (n = 1389). Relevant main associations and interactions by asthma and/or smoking on post‐BD forced expiratory volume in 1 s/forced vital capacity (FEV₁/FVC; continuous variable) and AO (FEV₁/FVC < lower limit of normal) were estimated by multiple regression.

Results

Sixty‐nine percent (n = 950) had a history of childhood measles. Childhood measles augmented the combined adverse effect of current clinical asthma and smoking at least 10 pack‐years on post‐BD FEV₁/FVC ratio in middle age (z‐score: −0.70 (95% CI: −1.1 to −0.3) vs −1.36 (−1.6 to −1.1), three‐way interaction: P = 0.009), especially for those with childhood‐onset asthma. For never‐ and ever‐smokers of <10 pack‐years who had current asthma symptoms, compared with those without childhood measles, paradoxically, the odds for post‐BD AO was not significant in the presence of childhood measles (OR: 12.0 (95% CI: 3.4–42) vs 2.17 (0.9–5.3)).

Conclusion

Childhood measles infection appears to compound the associations between smoking, current asthma and post‐BD AO. Differences between asthma subgroups provide further insight into the complex aetiology of obstructive lung diseases for middle‐aged adults.

     

The use of non‐invasive ventilation for life‐threatening asthma attacks: Changes in the need for intubation

Background and objective: Although non‐invasive ventilation (NIV) has been shown to be effective in a wide variety of respiratory diseases, its role in severe asthma attacks remains uncertain. The aim of this study was to clarify the effectiveness of NIV in patients experiencing severe attacks of asthma. Methods: A retrospective cohort study was performed, comparing the periods November 1999–October 2003 (pre‐introduction of NIV) and November 2004–October 2008 (post‐introduction of NIV). The data and clinical outcomes for patients who experienced severe attacks of asthma, and who fulfilled the inclusion criteria, were retrieved and compared. Results: Fifty events (48 patients) from the pre‐NIV period and 57 events (54 patients) from the post‐NIV period, which required hospitalization, were included in the analysis. Nine of the 50 pre‐NIV events (mean PaO₂/fraction of inspired O₂ (FiO₂) 241 ± 161; PaCO₂ 79 ± 40) were treated primarily by endotracheal intubation (ETI), while 17 of the 57 post‐NIV events (PaO₂/FiO₂ 197 ± 132, P = 0.39; PaCO₂ 77 ± 30, P = 0.95) were treated primarily by NIV. The rate of ETI decreased in the post‐NIV period (2/57 (3.5%) vs 9/50 (18%), P = 0.01). NIV was started earlier than mechanical ventilation (MV) with ETI (mean time interval between arrival and start of MV 171.7 ± 217.9 min vs 38.5 ± 113.8 min for NIV, P < 0.05). In the post‐NIV cohort, there was a trend towards a reduction in the duration of MV with ETI or NIV (36.9 ± 38.4 h vs 20.3 ± 35.8 h, P = 0.09), and hospital stay was shortened (12.6 ± 4.2 vs 8.4 ± 2.8 days, P < 0.01). No deaths occurred during this period as a consequence of asthma attacks. Conclusions: The need for ETI in patients with severe attacks of asthma was decreased after introduction of NIV. The ready availability of NIV enabled the rapid commencement of MV and may decrease the need for ETI. NIV is an acceptable and useful method of stabilizing patients experiencing severe attacks of asthma.     

Encephalitis caused by human herpesvirus‐6B in pancreas‐after‐kidney transplantation

Human herpesvirus‐6 (HHV‐6) is a common pathogen among children, classically presenting with fever and rash that resolves without specific therapy. HHV‐6 can be reactivated in the immunosuppressed patient. After bone marrow and solid organ transplantation, HHV‐6 has been linked to various clinical syndromes, including undifferentiated febrile illness, encephalitis, myelitis, hepatitis, pneumonitis, and bone marrow suppression. However, HHV‐6 encephalitis after pancreatic transplant has rarely been reported. Early diagnosis and treatment of HHV‐6 encephalitis may be important for affected patients. We report the case of a 53‐year‐old pancreas‐after‐kidney transplant recipient who initially presented with high fever and confusion 3 weeks after operation. We managed to save the patient's life and preserve the pancreas graft function. We also review previously reported cases of HHV‐6B encephalitis in solid organ transplant recipients.     

Experimental study for the mechanism of gastroesophageal‐reflux‐associated asthma

Epidemiologic studies have shown a strong association between gastroesophageal reflux (GER) and asthma, especially in children. Diagnosing GER can be difficult in some patients when GER presents solely with asthma. The aim of this study was to explore the relationship between GER and asthma with animal model. Sixty rats were randomly divided into six equal groups, GER group, GER‐associated‐asthma group, allergic asthma group, and their control groups. The cytokine levels and concentration of inflammatory cells in bronchoalveolar lavage (BAL) were determined. The BAL of the rats with allergic asthma contained higher concentration of Interleukin‐5 (IL‐5) and more eosinophils than those of rats with GER‐associated‐asthma. This demonstrates that assaying the concentrations of IL‐5 and inflammatory cells in BAL may be an effective method of distinguishing GER‐associated asthma from allergic asthma.