Regular use of non‐steroidal anti‐inflammatory drugs increases the risk of adult‐onset asthma: a population‐based follow‐up study

Background: Little is known about the relation between regular use of non‐steroidal anti‐inflammatory drugs (NSAIDs) and the risk of asthma at the population level. The aim of this study was to examine a possible association between intake of NSAIDs and risk of adult‐onset asthma. Methods: Using data from two multidisciplinary postal questionnaire surveys concerning health and lifestyle, we prospectively studied 19 349 adult twins enrolled in the nationwide Danish Twin Registry. Results: We found a higher prevalence of new‐onset asthma in subjects who used NSAIDs (other than aspirin) regularly compared with non‐users (7.7% vs 4.3%), OR = 1.87 (1.25–2.81), P = 0.002. The result remained significant after adjusting for sex, age, smoking, BMI, hay fever, eczema and intake of medications other than NSAIDs, OR = 1.90 (1.26–2.85), P = 0.002. Conclusions: Regular use of NSAIDs other than aspirin may be a risk factor for adult‐onset asthma. This observation must be accommodated in explanations of the relationship between use of analgesics and risk of asthma. Please cite this paper as: Thomsen SF, Kyvik KO, Skadhauge LR, Steffensen I and Backer V. Regular use of non‐steroidal anti‐inflammatory drugs increases the risk of adult‐onset asthma: a population‐based follow‐up study. The Clinical Respiratory Journal 2009; 3: 82–84.     

Utility of hypertonic histamine challenge in distinguishing difficult‐to‐diagnose asthma

Introduction: Although classical asthma is associated with airway hyperresponsiveness (AHR), this condition is also present in many cardiopulmonary disorders undermining the rational basis of its measurement in the differential diagnosis of asthma. We have recently introduced a new method to investigate AHR, the hypertonic histamine challenge (HHC). Objective: The aim of this study was to evaluate the differential diagnostic power of HHC in a clinically representative sample of 138 patients. Methods: Fifty‐seven patients from the outpatient clinic of the authors' hospital with symptoms indicative of asthma were consecutively recruited. Asthma was confirmed in 31 subjects. The remaining 26 subjects formed the control group, in conjunction with seven patients with COPD, 15 patients with interstitial lung disease, 21 patients with rhinitis, 13 patients with heart failure and 25 healthy controls. Hypertonic histamine solution was administered with an ultrasonic nebuliser. Results: Only the PC₂₀ values of asthmatic subjects differed statistically significantly from those of the healthy group (P < 0.0001). The receiver operator characteristic curve indicated that a PC₂₀ value of 0.83 mg/mL would be the optimal cut‐off point of HHC to separate the asthmatics from the symptomatic controls with a sensitivity of 81% and specificity of 70%. With the PC₂₀ values of 0.1 and 4.0 mg/mL, the sensitivities were 42% and 100%, and the specificities were 96% and 40%, respectively. In these limits, HHC either confirmed or excluded asthma in 64 out of 138 patients (46%). Conclusion: The authors' attempt to improve the accuracy of the airway challenge test by combining direct and indirect challenges did not overcome the diagnostic limitations of previously utilised airway challenges. Please cite this paper as: Purokivi M, Koskela HO, Koistinen T, Magga J, Peuhkurinen K, Kiviniemi V and Kontra KM. Utility of hypertonic histamine challenge in distinguishing difficult‐to‐diagnose asthma. The Clinical Respiratory Journal 2007; 1:91–98.     

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.

     

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.     

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.     

Pediatric obesity‐related asthma: A prototype of pediatric severe non‐T2 asthma

Childhood obesity contributes to many diseases, including asthma. There is literature to suggest that asthma developing as a consequence of obesity has a nonallergic or non‐T2 phenotype. In this review, obesity‐related asthma is utilized as a prototype of non‐T2 asthma in children to discuss several nonallergic mechanisms that underlie childhood asthma. Obesity‐related asthma is associated with systemic T helper (Th)1 polarization occurring with monocyte activation. These immune responses are mediated by insulin resistance and dyslipidemia, metabolic abnormalities associated with obesity, that are themselves associated with pulmonary function deficits in obese asthmatics. As in other multifactorial diseases, there is both a genetic and an environmental contribution to pediatric obesity‐related asthma. In addition to genetic susceptibility, differential DNA methylation is associated with non‐T2 immune responses in pediatric obesity‐related asthma. Initial investigations into the biology of non‐T2 immune responses have identified the upregulation of genes in the CDC42 pathway. CDC42 is a RhoGTPase that plays a key role in Th cell physiology, including preferential naïve Th cell differentiation to Th1 cells, and cytokine production and exocytosis. Although these novel pathways are promising findings to direct targeted therapy development for obesity‐related asthma to address the disease burden, there is evidence to suggest that dietary interventions, including diet modification, rather than caloric restriction alone, decrease disease burden. Adoption of a diet rich in micronutrients, including carotenoids and 25‐OH cholecalciferol, a vitamin D metabolite, may be beneficial since these are positively correlated with pulmonary function indices, while being protective against metabolic abnormalities associated with the obese asthma phenotype.     

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.