Asthma Events Research Articles

Spike in Asthma Healthcare Presentations in Eastern England during June 2021: A Retrospective Observational Study Using Syndromic Surveillance Data.

Thunderstorm asthma is often characterised by a sudden surge in patients presenting with exacerbated symptoms of asthma linked to thunderstorm activity. Here, we describe a large spike in asthma and difficulty breathing symptoms observed across parts of England on 17 June 2021. The number of healthcare presentations during the asthma event was compared to expected levels for the overall population and across specific regions. Across affected geographical areas, emergency department attendances for asthma increased by 560% on 17 June compared to the average number of weekday daily attendances during the previous 4 weeks. General practitioner out of hours contacts increased by 349%, National Health Service (NHS) 111 calls 193%, NHS 111 online assessments 581% and ambulance call outs 54%. Increases were particularly noted in patient age groups 5–14 and 15–44 years. In non-affected regions, increases were small (<10%) or decreased, except for NHS 111 online assessments where there was an increase of 39%. A review of the meteorological conditions showed several localised, weak, or moderate thunderstorms specifically across parts of Southeast England on the night of June 16. In this unprecedented episode of asthma, the links to meteorologically defined thunderstorm activity were not as clear as previous episodes, with less evidence of ‘severe’ thunderstorm activity in those areas affected, prompting further discussion about the causes of these events and implications for public health management of the risk.

Role of miR-185-5p as modulator of periostin synthesis and smooth muscle contraction in asthma.

Asthma is a chronic respiratory disease produced by an aberrant immune response that originates with breathing difficulties and cough, through airway remodeling. The above pathophysiological events of asthma emerge the regulators of effectors, like epigenetics, which include microRNAs (miRNAs) who perform post‐transcriptional regulation, controlling diverse pathways in respiratory diseases. The objective of the study was to determine how miR‐185‐5p regulates the secretion of periostin by airway structural cells, and smooth muscle cells contraction, both related to airway remodeling in asthma. We used miR‐185‐5p mimic and inhibitors in bronchial smooth muscle cells (BSMCs) and small airway epithelial cells (SAECs) from healthy subjects. Gene expression and protein levels of periostin (POSTN), CDC42, and RHOA were analyzed by RT‐PCR and ELISA/Western blot, respectively. BSMC contractility was analyzed using cell‐embedded collagen gels and measurement of intracellular calcium was performed using Fura‐2. Additionally, miR‐185‐5p and periostin expression were evaluated in sputum from healthy and asthmatics. From these experiments, we observed that miR‐185‐5p modulation regulates periostin mRNA and protein in BSMCs and SAECs. A tendency for diminished miR‐185‐5p expression and higher periostin levels was seen in sputum cells from asthmatics compared to healthy, with an inverse correlation observed between POSTN and miR‐185‐5p. Inhibition of miR‐185‐5p produced higher BSMCs contraction induced by histamine. Calcium mobilization was not modified by miR‐185‐5p, showing that miR‐185‐5p role in BSMC contractility is performed by regulating CDC42 and RhoA pro‐contractile factors instead. In conclusion, miR‐185‐5p is a modulator of periostin secretion by airway structural cells and of smooth muscle contraction, which can be related to asthma pathophysiology, and thus, might be a promising therapeutic target.

Occupations and exposure events in acute and subacute irritant-induced asthma

BackgroundExposures leading to irritant-induced asthma (IIA) are poorly documented.MethodsWe retrospectively screened the medical records of patients with IIA diagnosed in an occupational medicine clinic during 2000–2018. We classified the cases...

Influenza Vaccination Is Associated With Lower Incidental Asthma Risk in Patients With Atopic Dermatitis: A Nationwide Cohort Study.

BackgroundAtopic march refers to the natural history of atopic dermatitis (AD) in infancy followed by subsequent allergic rhinitis and asthma in later life. Respiratory viruses interact with allergic sensitization to promote recurrent wheezing and the development of asthma. We aimed to evaluate whether influenza vaccination reduces asthma risk in people with AD.MethodsThis cohort study was conducted retrospectively from 2000 to 2013 by the National Health Insurance Research Database (NHIRD). Patients with newly diagnosed AD (International Classification of Diseases, Ninth Revision, Clinical Modification code 691) were enrolled as the AD cohort. We matched each vaccinated patient with one non-vaccinated patient according to age and sex. We observed each participant until their first asthma event, or the end of the study on December 31, 2013, whichever came first.ResultsOur analyses included 4,414 people with a mean age of 53 years. Of these, 43.8 were male. The incidence density of asthma was 12.6 per 1,000 person-years for vaccinated patients, and 15.1 per 1000 person-years for non-vaccinated patients. The adjusted hazard ratio (aHR) of asthma in the vaccinated cohort relative to the non-vaccinated cohort was 0.69 (95% CI = 0.55–0.87). Vaccinated patients had a lower cumulative incidence of asthma than unvaccinated patients. Vaccinated participants in all age and sex groups trended toward a lower risk of asthma. People will reduce more asthma risk when taking shots every year.ConclusionInfluenza vaccination was associated with lower asthma risk in patients with AD.

Measuring the Association Between Thunderstorms in the Presence of High Pollen and Risk of Severe Asthma

BACKGROUND AND AIM: Studies have shown an acute association between the occurrence of thunderstorm conditions in the presence of high pollen and severe asthma, but minimal work has studied these events over a multi-year time series, using detailed measurements of storms and pollen. METHODS: We estimate the change in risk between thunderstorm asthma events and asthma-related emergency room visits in the Minneapolis-St. Paul metropolitan area for the years 2007-2018. We defined thunderstorm asthma events as daily occurrence of 2 or more lightning strikes during periods of high pollen, interpolated using weather and pollen monitor data and modeled lightning counts. Daily counts of asthma-related emergency department visits were acquired from the Minnesota Hospital Association. We use a 2-stage approach combining zip code level quasi-Poisson time-series regressions in a meta-analysis to estimate an overall relative risk of hospitalizations during thunderstorm asthma events. RESULTS:We observed a 4.4% (RR = 1.044; 95% CI (1.013,1.076), increase in asthma emergency department visits on the day of thunderstorm asthma event and a 3.2% (RR 1.032; 95% CI (1.003,1.062) increase on the day after the storm event. Our findings were robust to adjustment for temperature, humidity, wind, precipitation, ozone, PM2.5, day of week, and natural splines for seasonal variation in asthma cases. Occurrence of lightning alone or pollen alone shows no association with risk of severe asthma. CONCLUSIONS:Our results support an association between co-occurrence of lightning and pollen and risk of asthma hospitalization. This model, while previously described with specific epidemic events, has not been well studied in a time series model to evaluate long-term risk, using measurement of both lightning and pollen, and never using unique small area exposure assignment and outcome counts. Our findings indicate that thunderstorm asthma may be an unidentified environmental risk factor for severe asthma. KEYWORDS: asthma, pollen, thunderstorms, climate

The Perfect Storm: Thunderstorm-Related Asthma

Thunderstorm asthma refers to the increase in acute asthma symptoms during or immediately after severe storm activity, especially during certain seasons. Epidemic thunderstorm asthma occurs when large numbers of patients are affected by thunderstorm activity. These thunderstorm asthma cases can be anywhere from mild to severe symptoms and requiring serious medical attention. Epidemic thunderstorm asthma events emphasize the importance of preventative and ongoing asthma and allergic rhinitis identification and management along with community education and awareness. This review highlights the significant impact on the emergency medical system and the need for risk assessments, asthma action plans, and overall advanced emergency preparedness.

Estimation of Asthma Symptom Onset Using Internet Search Queries: Lag-Time Series Analysis.

BackgroundAsthma affects over 330 million people worldwide. Timing of an asthma event is extremely important and lack of identification of asthma increases the risk of death. A major challenge for health systems is the length of time between symptom onset and care seeking, which could result in delayed treatment initiation and worsening of symptoms.ObjectiveThis study evaluates the utility of the internet search query data for the identification of the onset of asthma symptoms.MethodsPearson correlation coefficients between the time series of hospital admissions and Google searches were computed at lag times from 4 weeks before hospital admission to 4 weeks after hospital admission. An autoregressive integrated moving average (ARIMAX) model with an autoregressive process at lags of 1 and 2 and Google searches at weeks –1 and –2 as exogenous variables were conducted to validate our correlation results.ResultsGoogle search volume for asthma had the highest correlation at 2 weeks before hospital admission. The ARIMAX model using an autoregressive process showed that the relative searches from Google about asthma were significant at lags 1 (P<.001) and 2 (P=.04).ConclusionsOur findings demonstrate that internet search queries may provide a real-time signal for asthma events and may be useful to measure the timing of symptom onset.

Atmospheric modelling of grass pollen rupturing mechanisms for thunderstorm asthma prediction.

The world's most severe thunderstorm asthma event occurred in Melbourne, Australia on 21 November 2016, coinciding with the peak of the grass pollen season. The aetiological role of thunderstorms in these events is thought to cause pollen to rupture in high humidity conditions, releasing large numbers of sub-pollen particles (SPPs) with sizes very easily inhaled deep into the lungs. The humidity hypothesis was implemented into a three-dimensional atmospheric model and driven by inputs from three meteorological models. However, the mechanism could not explain how the Melbourne event occurred as relative humidity was very low throughout the atmosphere, and most available grass pollen remained within 40 m of the surface. Our tests showed humidity induced rupturing occurred frequently at other times and would likely lead to recurrent false alarms if used in a predictive capacity. We used the model to investigate a range of other possible pollen rupturing mechanisms which could have produced high concentrations of SPPs in the atmosphere during the storm. The mechanisms studied involve mechanical friction from wind gusts, electrical build up and discharge incurred during conditions of low relative humidity, and lightning strikes. Our results suggest that these mechanisms likely operated in tandem with one another, but the lightning method was the only mechanism to generate a pattern in SPPs following the path of the storm. If humidity induced rupturing cannot explain the 2016 Melbourne event, then new targeted laboratory studies of alternative pollen rupture mechanisms would be of considerable value to help constrain the parameterisation of the pollen rupturing process.

Community Response to the Impact of Thunderstorm Asthma Using Smart Technology

BackgroundThe most severe thunderstorm asthma (TA) event occurred in Melbourne on the 21st November 2016 and during this period, daily pollen information was available and accessible on smart devices via an App. An integrated survey within the App allows users to self-report symptoms.ObjectiveTo explore patterns of symptom survey results during the period when the TA event occurred.MethodsSymptom data from the Melbourne Pollen Count and Forecast App related to asthma history, hay fever symptoms, and medication use was explored. A one-week control period before and after the event was considered. Chi-square tests and logistic regression were used to assess associations between sex, age, symptoms, and medication use.ResultsOf the 28,655 responses, during the 2016 pollen season, younger (18 to 40 years) males, with no hay fever and no asthma were the most single and regular responders. During the TA event for new users, sex was only significantly associated with hay fever (p = 0.008) of which 60.2% of females’ responses reported having hay fever, while 43% of males’ responses did not. Those with mild symptoms peaked during the TA event.ConclusionsMany individuals completed the survey on the app for the first time during the TA event indicating the potential of digital technologies to be used as indicators of health risk among populations at risk of TA events.

A Pilot Forecasting System for Epidemic Thunderstorm Asthma in Southeastern Australia

AbstractIn November 2016, an unprecedented epidemic thunderstorm asthma event in Victoria, Australia, resulted in many thousands of people developing breathing difficulties in a very short period of time, including 10 deaths, and created extreme demand across the Victorian health services. To better prepare for future events, a pilot forecasting system for epidemic thunderstorm asthma (ETSA) risk has been developed for Victoria. The system uses a categorical risk-based approach, combining operational forecasting of gusty winds in severe thunderstorms with statistical forecasts of high ambient grass pollen concentrations, which together generate the risk of epidemic thunderstorm asthma. This pilot system provides the first routine daily epidemic thunderstorm asthma risk forecasting service in the world that covers a wide area, and integrates into the health, ambulance, and emergency management sector. Epidemic thunderstorm asthma events have historically occurred infrequently, and no event of similar magnitude has impacted the Victorian health system since. However, during the first three years of the pilot, 2017–19, two high asthma presentation events and four moderate asthma presentation events were identified from public hospital emergency department records. The ETSA risk forecasts showed skill in discriminating between days with and without health impacts. However, even with hindsight of the actual weather and airborne grass pollen conditions, some high asthma presentation events occurred in districts that were assessed as low risk for ETSA, reflecting the challenge of predicting this unusual phenomenon.

Thunderstorm Asthma: Looking Back and Looking Forward.

Epidemic thunderstorm asthma has been reported to have occurred around twenty times over the past three decades in locations around the world. Thunderstorm asthma events are characterized by a significant increase in asthma presentations, which on occasion can overwhelm local medical services and result in fatalities. This review article presents the epidemiological data underpinning previous thunderstorm asthma events and analyzes what is known about the etiology of this unusual phenomenon. The evidence behind published risk factors, both at the individual and population level, is discussed. Research from the fields of allergy, pulmonology, meteorology, and climatology is drawn together and critically reviewed to surmise future predictions regarding thunderstorm asthma episodes. Finally, evidence-based individual, community, and environmentally targeted preventive strategies are presented.

Particulate matter and emergency visits for asthma: a time-series study of their association in the presence and absence of wildfire smoke in Reno, Nevada, 2013\u20132018

BackgroundHealth risks due to particulate matter (PM) from wildfires may differ from risk due to PM from other sources. In places frequently subjected to wildfire smoke, such as Reno, Nevada, it is critical to determine whether wildfire PM poses unique risks. Our goal was to quantify the difference in the association of adverse asthma events with PM on days when wildfire smoke was present versus days when wildfire smoke was not present.MethodsWe obtained counts of visits for asthma at emergency departments and urgent care centers from a large regional healthcare system in Reno for the years 2013–2018. We also obtained dates when wildfire smoke was present from the Washoe County Health District Air Quality Management Division. We then examined whether the presence of wildfire smoke modified the association of PM2.5, PM10–2.5, and PM10 with asthma visits using generalized additive models. We improved on previous studies by excluding wildfire-smoke days where the PM concentration exceeded the maximum PM concentration on other days, thus accounting for possible nonlinearity in the association between PM concentration and asthma visits.ResultsAir quality was affected by wildfire smoke on 188 days between 2013 and 2018. We found that the presence of wildfire smoke increased the association of a 5 μg/m3 increase in daily and three-day averages of PM2.5 with asthma visits by 6.1% (95% confidence interval (CI): 2.1–10.3%) and 6.8% (CI: 1.2–12.7%), respectively. Similarly, the presence of wildfire smoke increased the association of a 5 μg/m3 increase in daily and three-day averages of PM10 with asthma visits by 5.5% (CI: 2.5–8.6%) and 7.2% (CI: 2.6–12.0%), respectively. We did not observe any significant increases in association for PM10–2.5 or for seven-day averages of PM2.5 and PM10.ConclusionsSince we found significantly stronger associations of PM2.5 and PM10 with asthma visits when wildfire smoke was present, our results suggest that wildfire PM is more hazardous than non-wildfire PM for patients with asthma.

Association of adenotonsillectomy with asthma and upper respiratory infection: A nationwide cohort study.

Adenotonsillectomy is a common paediatric surgery for treating obstructed breathing or recurrent inflammation; however, the long-term health consequences on the developing immune system are unknown. This study investigated the potential association between adenotonsillectomy and the development of asthma and upper respiratory infections (URI). This propensity score-matched retrospective cohort study utilized data from the National Sample Cohort 2002-2013. In the asthma cohort, we used a Cox-proportional hazards model to analyze the hazard ratio (HR) of adenotonsillectomy for asthma events. In the URI cohort, equivalence testing of postoperative visits for URI was performed. The margin of equivalence of the difference was set at -0.5-0.5. Asthma incidence was 66.97/1000 person-years in children who underwent adenotonsillectomy and 30.43/1000 person-years in those who did not. Adjusted asthma HRs were 2.25 (95% confidence interval, 1.96-2.57) in the adenotonsillectomy vs. non-adenotonsillectomy groups. In a subgroup analysis, children aged 5-9 years living in metropolitan areas showed a higher incidence of subsequent asthma than those of other ages and areas. However, any significant difference between the groups in terms of URI events in the 1-11-year postoperative period was not identified. Adenotonsillectomy in children is associated with an increased incidence of asthma, with no significant impact on postoperative visits for URI.

Are convergence lines associated with high asthma presentation days? A case-control study in Melbourne, Australia

BackgroundIn epidemic thunderstorm asthma (ETSA) events a large number of people develop asthma symptoms over a short period of time. This is thought to occur because of a unique combination of high amounts of pollen and certain meteorological conditions. However, the exact cause and mechanism of epidemic thunderstorm asthma remains unclear. ObjectivesThe objective of this study was to test the hypothesis that convergence lines may be a causative factor in ETSA events, by investigating whether convergence line weather events are associated with the occurrence of high asthma presentations days during the Victorian grass pollen season (October–December). MethodsA case control method was used. All public hospitals within 75 km of the Melbourne weather radar were included, and data were taken from 2009 to 2017 during the Victorian grass pollen season. Cases hospital days were hospitals with a high number of asthma presentations within a 24-h period, and controls were hospitals with an expected number of asthma presentations. Exposure was defined as geographical proximity of a convergence line to the hospital case or control. ResultsEighty-one case hospital days and 157 hospital day controls were included in the study. The odds of exposure to a convergence line were significantly higher for cases than for controls at all exposure distances. At 4 km, 80 of the 81 cases had been exposed to a convergence line. ConclusionConvergence lines appear to be a necessary, but not sufficient, element in the cause of epidemic thunderstorm asthma. This is the first study to show a clear link between epidemic thunderstorm asthma and convergence lines.

Thunderstorm asthma medication management during an external emergency (Code Brown): An observational study of the impact of electronic prescribing and clinical documentation

BackgroundOn 21 November 2016, during a thunderstorm asthma event, an external disaster was called in our Emergency Department (ED), the first since comprehensive implementation of electronic clinical documentation. This study compared medication ordering and administration documentation during surge (thunderstorm asthma) and non-surge (control) conditions. MethodsRetrospective audit of ED patients presenting with asthma between 21 and 23 November 2016 (72-h thunderstorm asthma period) and equivalent 72-h periods of the preceding three weeks (control period). Demographic details, medical history and treatment were extracted from Cerner Millennium. ResultsDuring the thunderstorm asthma and control periods, 318 and 164 patients presented with respiratory symptoms; 302 (95.0%) and 27 (16.5%) were due to asthma, respectively. Salbutamol was ordered and administration signed on the Medication Administration Record for 122/302 (40.4%) thunderstorm asthma and 21/27 (77.8%) control patients (p<0.01). During the thunderstorm asthma period, 52/302 (17.2%) patients had no documentation on the Medication Administration Record or any ED notes of receiving salbutamol, whilst during the control periods 2/27 (7.4%) patients had no such documentation. Similar disparities with corticosteroids and ipratropium were identified. ConclusionQuality of medication documentation declined during surge conditions. These data have informed policies for future surge events, when higher risk medications might be required.

Efficacy and safety of inhalation budesonide in the treatment of pediatric asthma in the emergency department: a systematic review and meta-analysis

This study was aimed to evaluate the beneficial role of inhalation budesonide(BUD) in improving the pulmonary functions, and reducing the hospital admission rate, worsening of asthma and commonly encountered adverse events in pediatric asthma. The electronic search was performed using PubMed, Scopus, CENTRAL (Cochrane Central Register of Controlled Trials) and Google scholar databases to identify the randomized control trials(RCTs). 21 RCTs involving 12,787 subjects were included. The meta-analysis revealed that the BUD has reduced the hospitalization rate (Mantel-Haenszel (M-H), random effects odd ratio (RE-OR) of 0.34, p = 0.003, I2 = 75%), and worsening of asthma (M-H, RE-OR 0.38, p = 0.001, I2 = 73%); significantly improved the pulmonary functions such as FEV1 (Inverse variance (IV): 1.05, p < 0.0001, I2 = 94%), PEFR (IV: 1.40, p < 0.0001, I2 = 87%), morning PEF (IV: 1.04, p < 0.0001, I2 = 91%), and evening PEF (IV: 1.29, p < 0.0001, I2 = 92%) compared to control. Further, the incidences of adverse events like Pharyngitis (M-H, RE-OR 0.88, at 95% CI, p = 0.69, I2 = 0%), Sinusitis (M-H, RE-OR 0.78, p = 0.79, I2 = 0%), Respiratory infections (M-H, RE-OR 0.96, p = 0.46, I2 = 0%), Otitis media (M-H, RE-OR 0.82, p = 0.32, I2 = 12%) and Fever (M-H, RE-OR 0.78, p = 0.64, I2 = 0%) were almost same between BUD and control. The outcomes of the meta-analysis suggest that high-dose inhalation BUD could benefit the pediatric patients in minimizing the worsening of asthma and hospitalization rate, along with improving the pulmonary functions, with negligible adverse drug reactions.

Lung mechanical properties distinguish children with asthma with normal and diminished lung function

Children with asthma, even those with severe persistent disease, can have forced expiratory volume in 1second (FEV1 ) values ≥100% of predicted, while others have diminished FEV1 . We sought to characterize the lung mechanical properties underlying these two asthma phenotypes and the mechanisms explaining the paradox of severe asthmatic children, whom when clinically stable can have an FEV1 >100% of predicted, but during an acute bronchospastic episode can experience a life-threatening asthma event. Lung mechanics were evaluated in three groups of children: asthmatics with FEV1 ≥100% (HFEV1 ; n=13), asthmatics with FEV1 ≤80% (LFEV1 ; n=14) and non-asthmatic controls (n=10). A linear mixed model was used to examine the relationship between volume and static transpulmonary pressures obtained at total lung capacity (TLC); actual TLC %of predicted and flow; and static transpulmonary pressure and flow. HFEV1 asthmatics had larger airways (FEV1 z-scores 1.12 vs -2.37; P<.05), greater lung volumes (mean % of predicted TLC 134.8% vs 109.6%; P<.05) and lower airway resistance (mean %of predicted Raw 101.9% vs 199.9%; P<.05) compared to the LFEV1 group. Moreover, HFEV1 asthmatics had significantly reduced elastic recoil pressure (pressure-volume curve shifted upward and to the left) and higher lung compliance (0.21 vs 00.9L/cm H2 O; P<.05) compared to the LFEV1 group. The pressure-flow curves revealed the LFEV1 group to have significantly increased resistance to flow in the upstream segment of the airways at all lung volumes studied compared to HFEV1 . HFEV1 asthmatic children display distinct lung mechanical proprieties compared to their LFEV1 asthmatic peers. With loss of elastic recoil pressure, the HFEV1 group could generate normal FEV1 due to proportionally enlarged airways and reduced airway resistance, while airflow limitation in the LFEV1 is due to increased airway resistance. Loss of elastic recoil and interdependence during acute bronchoconstriction episodes may predispose the HFEV1 group to catastrophic reductions in airflow.

Letter to the editor - serious asthma events with fluticasone plus salmeterol versus fluticasone alone

Letter to the editor - serious asthma events with fluticasone plus salmeterol versus fluticasone alone

Natural history of asthma symptoms after epidemic thunderstorm asthma: a 3-year longitudinal study.

BackgroundThe world's most catastrophic epidemic thunderstorm asthma event (ETSA) affected Melbourne in 2016. Little is known about the natural history of individuals affected by such extreme events.ObjectiveIn this single center prospective 3-year longitudinal study, symptomatology and behaviors of individuals affected by ETSA were assessed.MethodsStandardized telephone questionnaire was used to evaluate frequency of asthma symptoms, inhaled corticosteroid preventer use, asthma action plan ownership, and healthcare utilization. Questionnaires were administered at 12, 24, and 36 months after 2016 ETSA. Subgroup analyses of the ‘current’, ‘past’, ‘possible,’ and ‘no asthma’ subgroups were also conducted.ResultsTwo hundred and eight, 164, and 112 completed questionnaires were analyzed in 2017, 2018, and 2019, respectively. Seventy to eighty five percent of respondents reported ongoing asthma symptoms in any given year, of which 20%–28% experienced weekly symptoms. Nearly 50% of respondents were prescribed preventers, with approximately 45% adherent at least 5 days a week. Less than 40% had an asthma action plan and 15%–20% sought urgent medical attention for asthma over the follow-up period. Among 106 individuals with 3 consecutive years of completed questionnaires, those with no prior doctor diagnosis of asthma were significantly more likely to be asymptomatic on follow-up than those with a prior doctor diagnosis of asthma (p = 0.02). Subgroup analyses suggest that large proportions of respondents with ‘past’ and ‘no asthma’ continue to remain symptomatic throughout the 36-month period.ConclusionIn individuals affected by ETSA, we found evidence of ongoing loss of asthma control in those with previously well controlled asthma, and the persistence of symptoms suggestive of asthma in those with no history or symptoms suggestive of prior asthma, even after 36 months from initial ETSA. Low rates of inhaler adherence and asthma action plan ownership may contribute to increased morbidity and mortality from future ETSA events. Further research is required to confirm these findings.

A long-term clinical trial on the efficacy and safety profile of doxofylline in Asthma: The LESDA study

Doxofylline, an oral methylxanthine with bronchodilator and anti-inflammatory activities, offers a promising alternative to theophylline due to its superior efficacy/safety profile. No long-term studies on the efficacy and safety of doxofylline are currently available in asthma. The aim of the Long-term clinical trial on the Efficacy and Safety profile of Doxofylline in Asthma (LESDA) study was to investigate the safety and efficacy profile of doxofylline administered for one year in asthmatic patients. LESDA was a multicenter, open-label, Phase III, clinical trial in which adult asthmatic patients received the same treatment (oral doxofylline 400 mg t.i.d.) for one year. Efficacy was assessed through periodic pulmonary function tests and by having the subjects keep monthly records of asthma events rates and use of salbutamol as rescue medication. The rate of adverse events (AEs) was recorded during the study.Three-hundred nine patients were screened and allocated in the study. Doxofylline significantly improved the change from baseline in forced expiratory volume in 1 s (FEV1) (+16.90 ± 1.81%, P < 0.001 vs. baseline). Doxofylline also significantly improved the rate of asthma events (events/day: -0.57 ± 0.18, P < 0.05 vs. baseline) and the use of salbutamol as rescue medication (puffs/day: -1.48 ± 0.25, P < 0.01 vs. baseline). The most common AEs were nausea (14.56%), headache (14.24%), insomnia (10.68%), and dyspepsia (10.03%). There were neither serious AEs nor deaths during or shortly after the study. Concluding, doxofylline is effective and well tolerated when administered chronically in asthmatic patients.