A critical analysis of the effect of OM-85 for the prevention of recurrent respiratory tract infections or wheezing/asthma from systematic reviews with meta-analysis.

Acute respiratory tract infections (RTIs) are one of the most common causes of pediatric consultations/hospitalizations and a major trigger for asthma exacerbations. Some consensus statements have recommended the use of immunostimulants to boost natural defenses against severe or repeated infections. One of the most common immunostimulants is OM-85; while several randomized clinical trials (RCTs) have evaluated its efficacy in preventing acute RTIs and wheezing/asthma exacerbations, results have been conflicting. Similarly, various systematic reviews with meta-analyses (SRMs) on OM-85 have used different strategies, populations, and outcomes; moreover, SRM conclusions are limited when the original studies are highly heterogeneous or have a low quality, hindering the generalizability of the findings. Here we summarize the evidence on the effect of OM-85 to prevent acute RTIs, wheezing/asthma episodes, or loss of asthma control in children, by including and critically evaluating all SRMs published to date. We searched for SRMs on OM-85 in three publication databases and found nine SRMs (seven for RTI, and two for wheezing/asthma). Among those, one had a high confidence evaluation of quality (AMSTAR-2 tool) and found a reduction in the total number of acute RTIs among the OM-85 group. Overall, no strong recommendations can be derived from the existing literature, mainly due to the high heterogeneity among included RCTs and SRMs. Further, large, high-quality RCTs are needed to confirm the true efficacy of OM-85 for the prevention of acute RTIs, asthma development, and asthma exacerbations.

Azithromycin therapy in infants hospitalized for respiratory syncytial virus bronchiolitis: Airway matrix metalloproteinase-9 levels and subsequent recurrent wheeze.

BACKGROUND: Early life respiratory syncytial virus (RSV) bronchiolitis is a significant risk factor for childhood asthma. In vitro and in vivo studies suggested that decreasing levels of airway matrix metalloproteinase (MMP)-9 during RSV bronchiolitis may be associated with clinical benefits. OBJECTIVE: To investigate whether azithromycin therapy during severe RSV bronchiolitis reduces upper airway MMP-9 levels, whether upper airway MMP-9 levels correlate with upper airway interleukin IL-8 levels, and whether MMP-9 level reduction is associated with reduced post-RSV recurrent wheeze (RW). METHODS: A total of 200 otherwise healthy 1- to 18-month-old infants hospitalized with RSV bronchiolitis were randomized into a double-blind, placebo-controlled trial of oral azithromycin (10 mg/kg daily for 7 days followed by 5 mg/kg daily for 7 days) or placebo. Infants were followed for 2 to 4 years for the outcome of RW (3 or more wheezing episodes). Nasal lavage samples for MMP-9 levels were obtained at baseline, day 14 (end of the study treatment), and after 6 months. RESULTS: Upper airway MMP-9 levels were highly correlated with IL-8 levels at all 3 time points: randomization, day 14, and 6 months (r = 0.80; P < .0001 for all time points). MMP-9 levels were similar between treatment groups at randomization, were lower on day 14 among children treated with azithromycin (P = .0085), but no longer different after 6 months. MMP-9 levels at baseline and change from baseline to day 14 were not associated with the development of RW (P = .49, .39, respectively). CONCLUSION: Azithromycin therapy in children hospitalized with RSV bronchiolitis had a short-term anti-inflammatory effect in reducing upper airway MMP-9 levels. However, the reduction in MMP-9 levels did not relate to subsequent RW post-RSV. TRIAL REGISTRATION: This study is a secondary analysis of the Azithromycin to Prevent Wheezing following severe RSV bronchiolitis-II clinical trial registered at Clinicaltrials.gov (NCT02911935).

Managing children with frequent respiratory infections and associated wheezing: a preliminary randomized study with a new multicomponent nasal spray.

BACKGROUND: Preschoolers frequently have respiratory infections (RIs), which may cause wheezing in some subjects. Type 2 polarization may favor increased susceptibility to RIs and associated wheezing. Non-pharmacological remedies are garnering increasing interest as possible add-on therapies. The present preliminary study investigated the efficacy and safety of a new multi-component nasal spray in preschoolers with frequent RIs and associated wheezing. METHODS: Some preschoolers with these characteristics randomly took this product, containing lactoferrin, dipotassium glycyrrhizinate, carboxymethyl-beta-glucan, and vitamins C and D3 (Saflovir), two sprays per nostril twice daily for 3 months. Other children were randomly treated only with standard therapy. Outcomes included the number of RIs and wheezing episodes, use of medications, and severity of clinical manifestations. RESULTS: Preschoolers treated add-on with this multicomponent product experienced fewer RIs and used fewer beta-2 agonists than untreated children (P = 0.01 and 0.029, respectively). CONCLUSIONS: This preliminary study demonstrated that a multicomponent product, administered add-on as a nasal spray, could reduce the incidence of RIs and use of symptomatic drugs for relieving wheezing in children.

Six-Year Follow-up of a Trial of Antenatal Vitamin D for Asthma Reduction.

BACKGROUND: We previously reported the results of a trial of prenatal vitamin D supplementation to prevent asthma and recurrent wheeze in young children, which suggested that supplementation provided a protective effect at the age of 3 years. We followed the children through the age of 6 years to determine the course of asthma and recurrent wheeze. METHODS: In this follow-up study, investigators and participants remained unaware of the treatment assignments through the children's sixth birthday. We aimed to determine whether, when maternal levels of 25-hydroxyvitamin D were taken into account, children born to mothers who had received 4400 IU of vitamin D3 per day during pregnancy (vitamin D group) would have a lower incidence of asthma and recurrent wheeze at the age of 6 years than would those born to mothers who had received 400 IU of vitamin D3 per day (control group). Time-to-event methods were used to compare the treatment groups with respect to time to the onset of asthma or recurrent wheeze. Multivariate methods were used to compare longitudinal measures of lung function between the treatment groups. RESULTS: There was no effect of maternal vitamin D supplementation on asthma and recurrent wheeze in either an intention-to-treat analysis or an analysis with stratification according to the maternal 25-hydroxyvitamin D level during pregnancy. There was no effect of prenatal vitamin D supplementation on most of the prespecified secondary outcomes. We found no effects of prenatal supplementation on spirometric indexes. Although there was a very small effect on airway resistance as measured by impulse oscillometry, this finding was of uncertain significance. CONCLUSIONS: Vitamin D supplementation during the prenatal period alone did not influence the 6-year incidence of asthma and recurrent wheeze among children who were at risk for asthma. (Funded by the National Heart, Lung, and Blood Institute; VDAART ClinicalTrials.gov number, NCT00920621.).

Efficacy of inhaled salbutamol with and without prednisolone for first acute rhinovirus-induced wheezing episode.

BACKGROUND: Acute rhinovirus-induced wheezing is common in young children and may respond to systemic corticosteroid. There are no trials on the efficacy of inhaled beta2 -agonist in this clinical scenario. OBJECTIVE: To study post hoc the short-term (up to 2 months) efficacy of inhaled beta2 -agonist with and without oral corticosteroid in the first acute rhinovirus-induced severe wheezing episode in young hospitalized children. METHODS: The study population came from two randomized controlled trials comparing oral prednisolone (2 mg/kg/d for 3 days) to placebo: Vinku (n = 35, NCT00494624) used high-dose regular nebulized salbutamol (0.15 mg/kg 2-4 h intervals) and Vinku2 (n = 60, NCT00731575, EudraCT 2006-007100-42) used inhaled salbutamol on-demand. Both studies used identical detailed follow-up assessments. The primary outcome of the former was the duration of hospitalization and of the latter the occurrence of and the time to a new physician-confirmed wheezing episode within 2 months after discharge. Treatment groups included salbutamol high-dose vs. salbutamol on-demand while adjusting for prednisolone status and acknowledging for interactions with exception of the duration of hospitalization in which prednisolone groups could not be fully used due to protocol differences. RESULTS: Median age of subjects was 13 months, 32% were sensitized and 22% had doctor-diagnosed eczema. In the duration of hospitalization, salbutamol high-dose/placebo versus salbutamol on-demand/placebo groups did not differ (p = .12). In the occurrence of and time to relapse within 2 months, a significant group × treatment interaction was observed (both p = .02), such that high-dose group had less and longer time to relapses than on-demand group in prednisolone arm (both p < .05), but no difference was detected in placebo arm (both p > .26). CONCLUSIONS: In young, hospitalized children with first episode of rhinovirus-induced wheezing, high-dose inhaled salbutamol may interact with oral prednisolone. However, further trials are warranted.

Inhaled corticosteroids for the prevention of asthma exacerbations.

OBJECTIVE: To provide an overview of the risk factors and mechanisms underlying asthma exacerbations and the role of inhaled corticosteroids (ICSs) in preventing exacerbations. DATA SOURCES: Queries for asthma exacerbations and ICSs were conducted using PubMed, searching for primary articles and reviews. STUDY SELECTIONS: Studies written in English, with a focus on well-designed randomized controlled clinical trials. RESULTS: Asthma exacerbations remain a major source of morbidity, with future exacerbations most likely among patients with previous exacerbations and among those with peripheral blood eosinophilia. Exacerbations are often triggered by viral respiratory tract infections, but recent evidence supports nonviral triggers as well. In terms of exacerbation prevention, several approaches to ICS therapy have been found to be effective, including intermittent high-dose ICS without use of background controller in preschool children with recurrent episodic wheezing, intermittent high-dose ICS without use of background controller in adults with mild asthma, and as-needed ICS dosing whenever rescue treatment is needed among children, adolescents, and adults with mild asthma not receiving daily controller therapy. CONCLUSION: ICSs are highly effective in preventing exacerbations of asthma. Multiple dosing strategies have been found to reduce exacerbation risk, allowing for a personalization of approaches based on individual patient phenotypes and preferences.

Intravenous magnesium sulphate in children with acute wheeze: a nationwide survey.

OBJECTIVE: Dutch guidelines recommend to consider intravenous magnesium sulfate (iv MgSO4) as a treatment option in case of failure of first line treatment in both children with exacerbations of acute episodic viral wheeze (AEVW) and acute asthma (AA). The implications on the actual use of iv MgSO4 iv in daily practice in both groups are unknown. Therefore, we conducted a cross-sectional nationwide survey to evaluate the use of iv MgSO4 in children with AEVW and AA. METHODS: A questionnaire was handed out to pediatricians and pediatric residents in one academic and six community teaching hospitals. RESULTS: In 111 respondents, 76% reported regular use of iv MgSO4 in children with AEVW and 96% in children with AA. In total 89% and 93% of users were convinced iv MgSO4 was effective in children with AEVW and AA, respectively. Adverse effects, mainly hypotension, were identified by 23% and 17% of users in AEVW and AA, respectively. Most common reasons not to give MgSO4 were lack of evidence and small amount of studies. CONCLUSIONS: IV MgSO4 is reported to be widely used in Dutch practice in both young children with AEVW and older children with AA by respondents, while the national guidelines advise only to consider this treatment option.

Effect of Prophylactic Subcutaneous Scopolamine Butylbromide on Death Rattle in Patients at the End of Life: The SILENCE Randomized Clinical Trial.

Importance: Death rattle, defined as noisy breathing caused by the presence of mucus in the respiratory tract, is relatively common among dying patients. Although clinical guidelines recommend anticholinergic drugs to reduce the death rattle after nonpharmacological measures fail, evidence regarding their efficacy is lacking. Given that anticholinergics only decrease mucus production, it is unknown whether prophylactic application may be more appropriate. Objective: To determine whether administration of prophylactic scopolamine butylbromide reduces the death rattle. Design, Setting, and Participants: A multicenter, randomized, double-blind, placebo-controlled trial was performed in 6 hospices in the Netherlands. Patients with a life expectancy of 3 or more days who were admitted to the participating hospices were asked to give advance informed consent from April 10, 2017, through December 31, 2019. When the dying phase was recognized, patients fulfilling the eligibility criteria were randomized. Of the 229 patients who provided advance informed consent, 162 were ultimately randomized. The date of final follow-up was January 31, 2020. Interventions: Administration of subcutaneous scopolamine butylbromide, 20 mg four times a day (n = 79), or placebo (n = 78). Main Outcomes and Measures: The primary outcome was the occurrence of a grade 2 or higher death rattle as defined by Back (range, 0-3; 0, no rattle; 3, rattle audible standing in the door opening) measured at 2 consecutive time points with a 4-hour interval. Secondary outcomes included the time between recognizing the dying phase and the onset of a death rattle and anticholinergic adverse events. Results: Among 162 patients who were randomized, 157 patients (97%; median age, 76 years [IQR, 66-84 years]; 56% women) were included in the primary analyses. A death rattle occurred in 10 patients (13%) in the scopolamine group compared with 21 patients (27%) in the placebo group (difference, 14%; 95% CI, 2%-27%, P = .02). Regarding secondary outcomes, an analysis of the time to death rattle yielded a subdistribution hazard ratio (HR) of 0.44 (95% CI, 0.20-0.92; P = .03; cumulative incidence at 48 hours: 8% in the scopolamine group vs 17% in the placebo group). In the scopolamine vs placebo groups, restlessness occurred in 22 of 79 patients (28%) vs 18 of 78 (23%), dry mouth in 8 of 79 (10%) vs 12 of 78 (15%), and urinary retention in 6 of 26 (23%) vs 3 of 18 (17%), respectively. Conclusions and Relevance: Among patients near the end of life, prophylactic subcutaneous scopolamine butylbromide, compared with placebo, significantly reduced the occurrence of the death rattle. Trial Registration: trialregister.nl Identifier: NTR6264.

Change in the symptom profile treated as asthma - two cross-sectional studies twenty years apart.

AIMS: The aims of the study were to investigate prevalence trends of respiratory symptoms, asthma and asthma treatment among young adults in Estonia and to estimate changes in symptom profile among subjects who self-report asthma attacks or use asthma medications. METHODS: Two similar questionnaires on respiratory health were sent to subjects in Tartu, Estonia, aged between 20 and 44 years; first in 1993/94, and then in 2014/15. To study the impact of different respiratory symptoms on asthma diagnosis and treatment, the log-binomial regression was used to estimate the association between 'attack of asthma' (as a proxy for current asthma) and respiratory symptoms as well as asthma treatment and respiratory symptoms, adjusted for age, sex and smoking history. RESULTS: Self-reported prevalence of asthma attack, asthma medication use and nasal allergies increased over the twenty years between studies, whereas there was no change in prevalence of asthma-related symptoms, and the prevalence of most respiratory symptoms either decreased, or remained unchanged. For women experiencing asthma attacks, the prevalence of nasal allergies increased and waking with chest tightness decreased. For men using asthma medication, the prevalence of a wheeze without a cold decreased. Women using asthma medication reported decreased prevalence of waking with chest tightness. CONCLUSION: Self-reported asthma attacks and asthma medication use has increased in last 20 years, while the prevalence of most respiratory symptoms either decreased or did not change. It is likely that changes in asthma symptom profile have had an impact on the prevalence of asthma and asthma treatment.

Cross-Sectional Association of Lifetime Electronic Cigarette Use with Wheezing and Related Respiratory Symptoms in U.S. Adults.

INTRODUCTION: Electronic cigarette use (vaping) has been found to be associated with respiratory symptoms like wheezing or whistling in the chest. Whether or not lifetime vaping occurrences are associated with wheezing has not yet been investigated. METHODS: Population Assessment of Tobacco and Health (PATH) Study Wave 4 data with 22,233 adults collected from December 2016 to January 2018 were used. The cross-sectional association of lifetime vaping occurrences with wheezing and related respiratory symptoms was examined using multivariable weighted logistic regression models considering the complex sampling design. RESULTS: According to the weighted PATH Wave 4 data, about 89.9% adults never vaped, 3.2% adults vaped one time, 3.2% vaped 2-10 times, 1.3% vaped 11-20 times, 1.1% vaped 21-50 times, 0.4% vaped 51-99 times, and 0.9% vaped 100 or more times in their entire life. Compared to adults who never vaped, adults who vaped 2-10 times had a significantly higher association with ever wheezing (aOR = 1.4, 95% CI: 1.1 to 1.6), past 12-month wheezing (aOR = 1.5, 95% CI: 1.2 to 1.9) and the number of wheezing attacks in the past 12 months (aOR = 1.5, 95% CI: 1.2 to 1.8). Adults who vaped 11-20 times and 100 or more times had similar associations with wheezing as that for adults who vaped 2-10 times. Controlling other tobacco use attenuated the associations. CONCLUSIONS: Lifetime vaping occurrences were found to be associated with some definitions of self-reported wheezing in cross-sectional analyses adjusted for other tobacco use. IMPLICATIONS: Using the cross-sectional PATH Wave 4 data with 22,233 adults, we found significant associations between lifetime vaping occurrences and ever wheezing or whistling in the chest, past 12 months wheezing or whistling in the chest, as well as the number of wheezing attacks in the past 12 months. The study results suggest that larger studies with more precise time frames and measures are needed to further understand possible connections between vaping experimentation and wheezing symptoms that could inform our understanding of the health effects of electronic cigarettes and resultant policy decisions.

Cross-Sectional Association Between Exclusive and Concurrent Use of Cigarettes, ENDS, and Cigars, the Three Most Popular Tobacco Products, and Wheezing Symptoms Among U.S. Adults.

INTRODUCTION: This study assessed the association of exclusive and concurrent use of cigarettes, electronic nicotine delivery systems (ENDS), and cigars with ever and past 12-month wheezing symptoms among a nationally representative sample of US adult current tobacco users. METHODS: Cross-sectional data from the Population Assessment of Tobacco and Health (PATH) Study Wave 3 (W3) were used. The weighted prevalence of self-reported ever and past 12-month wheezing symptoms for noncurrent users compared with users of cigarettes, ENDS, cigars, and any combination of these products (polytobacco use of these tobacco products) were presented for 28 082 adults. The cross-sectional association of tobacco use with self-reported wheezing symptoms was assessed using weighted multivariable and ordinal logistic regression with consideration of complex sampling design. RESULTS: Significantly higher odds of ever had wheezing or whistling in the chest at any time in the past were observed among current cigarette (adjusted odds ratio: 2.62, 95% confidence intervals [CI]: 2.35, 2.91), ENDS (1.49, 95% CI: 1.14, 1.95), and polytobacco users (2.67, 95% CI: 2.26, 3.16) compared with noncurrent users. No associations were seen for cigar use. Polytobacco use was associated with a higher odds of ever wheezing when compared with exclusive ENDS (1.61, 95% CI: 1.19, 2.17) and exclusive cigar use (2.87, 95% CI: 1.93, 4.26), but not exclusive use of cigarettes. CONCLUSIONS: Ever wheezing is associated with the use of cigarettes, ENDS, and polytobacco use of cigarettes, ENDS, and/or cigars, but not cigar use. The association of polytobacco use and wheezing appears to be driven by cigarette use. IMPLICATIONS: Cross-sectional associations with ever and past 12-month wheezing symptoms were found to be the strongest among cigarette users, exclusively or in combination. Future longitudinal research is needed to better understand how cigarette use interacts with other tobacco and nicotine products and contributes to respiratory symptoms.

Fish Oil-Derived Fatty Acids in Pregnancy and Wheeze and Asthma in Offspring.

BACKGROUND: Reduced intake of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) may be a contributing factor to the increasing prevalence of wheezing disorders. We assessed the effect of supplementation with n-3 LCPUFAs in pregnant women on the risk of persistent wheeze and asthma in their offspring. METHODS: We randomly assigned 736 pregnant women at 24 weeks of gestation to receive 2.4 g of n-3 LCPUFA (fish oil) or placebo (olive oil) per day. Their children formed the Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010) cohort and were followed prospectively with extensive clinical phenotyping. Neither the investigators nor the participants were aware of group assignments during follow-up for the first 3 years of the children's lives, after which there was a 2-year follow-up period during which only the investigators were unaware of group assignments. The primary end point was persistent wheeze or asthma, and the secondary end points included lower respiratory tract infections, asthma exacerbations, eczema, and allergic sensitization. RESULTS: A total of 695 children were included in the trial, and 95.5% completed the 3-year, double-blind follow-up period. The risk of persistent wheeze or asthma in the treatment group was 16.9%, versus 23.7% in the control group (hazard ratio, 0.69; 95% confidence interval [CI], 0.49 to 0.97; P=0.035), corresponding to a relative reduction of 30.7%. Prespecified subgroup analyses suggested that the effect was strongest in the children of women whose blood levels of eicosapentaenoic acid and docosahexaenoic acid were in the lowest third of the trial population at randomization: 17.5% versus 34.1% (hazard ratio, 0.46; 95% CI, 0.25 to 0.83; P=0.011). Analyses of secondary end points showed that supplementation with n-3 LCPUFA was associated with a reduced risk of infections of the lower respiratory tract (31.7% vs. 39.1%; hazard ratio, 0.75; 95% CI, 0.58 to 0.98; P=0.033), but there was no statistically significant association between supplementation and asthma exacerbations, eczema, or allergic sensitization. CONCLUSIONS: Supplementation with n-3 LCPUFA in the third trimester of pregnancy reduced the absolute risk of persistent wheeze or asthma and infections of the lower respiratory tract in offspring by approximately 7 percentage points, or one third. (Funded by the Lundbeck Foundation and others; ClinicalTrials.gov number, NCT00798226 .).

Vitamin D for secondary prevention of acute wheeze attacks in preschool and school-age children.

INTRODUCTION: Vitamin D is best known for its role in bone health; however, the discovery of the vitamin D receptor and the expression of the gene encoding the vitamin D 1α-hydroxylase (CYP27B1) enzyme in a wide variety of tissues including immune cells and respiratory epithelium has led to the discovery of potential roles for vitamin D in the prevention of acute wheeze. METHODS: We review here the literature concerning the relationships between circulating 25-hydroxyvitamin D (25(OH)D) concentration and secondary prevention of acute wheeze attacks in preschool and school-age children. RESULTS: Epidemiological data suggest that vitamin D insufficiency (25(OH)D <75 nmol/L) is highly prevalent in preschool and school-age children with wheeze. Preschool age children with a history of wheeze attacks and circulating 25(OH)D <75 nmol/L are at increased risk and frequency of future acute wheeze. However, no consistent association between low vitamin D status and risk of acute wheeze is reported in school-age children. Seven randomised controlled trials (RCTs) with relatively small sample sizes (30-430) and variable quality showed inconsistent results regarding the effect of oral vitamin D supplementation during childhood on the risk of asthma attacks, asthma symptom control, inhaled corticosteroid requirements, spirometry and unscheduled healthcare attendances for wheeze. A RCT showed that vitamin D supplementation had no effect on the frequency of unplanned healthcare attendances due to acute wheeze in 22 preschool children. DISCUSSION: An evidence-based recommendation for the use of vitamin D as a preventive therapy for wheeze attacks cannot be made until results of further trials are available. The assessment of circulating 25(OH)D concentration and the optimisation of vitamin D status to prevent acute respiratory tract infections, and to maintain skeletal and general health in preschool and school-age children with acute wheeze is worthwhile in its own right, but whether this will reduce the risk of acute wheeze attacks is unclear.

Vitamin D supplementation during pregnancy and the risk of wheezing in offspring: a systematic review and dose-response meta-analysis.

Background: In the past few years, growing evidence supports a preventive role of vitamin D supplementation during pregnancy for wheezing or asthma in offspring. However, the optimal dose of vitamin D intake is unclear. We conducted a meta-analysis to examine the linear and nonlinear dose-response pattern of vitamin D intake during pregnancy and asthma or wheezing in offspring. Questions/purposes: The purpose of this study was to answer the following question: Which dose of vitamin D is more effective in preventing wheezing in offspring? Method: We identified relevant studies by searching PubMed, EMBASE and CENTRAL up to December 2017 and by hand-searching reference lists. Meta-analysis and subgroup analysis were performed. Fixed or random effects model linear trends analyses were conducted based on the heterogeneity test. Then, if the data did not show linear trends, we considered a nonlinear trend analysis instead. Results: A total of 6068 participants were included in the study. Our analysis showed an inverse relationship between the intake of vitamin D during pregnancy and the occurrence of wheezing in offspring (pooled OR = 0.68, 95% CI = 0.55-0.83, I2 = 24%, Z statistic = 3.64, p < 0.01). We found a nonlinear U-shaped association between vitamin D supplementation during pregnancy and asthma or wheezing in offspring, with the lowest risk at approximately 800 IU/d. Publication bias was shown in a funnel plot without Egger's test. Conclusions: Vitamin D intake during pregnancy is inversely related to wheezing or asthma in offspring. Furthermore, the trend analysis indicates that offspring may benefit from approximately 800 IU/d vitamin D intake during pregnancy.

Omega-3 fatty acid intake and prevalent respiratory symptoms among U.S. adults with COPD.

BACKGROUND: Omega-3 fatty acids, including alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and derivatives, play a key role in the resolution of inflammation. Higher intake has been linked to decreased morbidity in several diseases, though effects on respiratory diseases like COPD are understudied. METHODS: The National Health and Nutrition Examination Survey (NHANES), with a focus on dietary assessment, provides a unique opportunity to explore relationships between omega-3 intake and morbidity in respiratory diseases marked by inflammation in the United States (US) population. We investigated relationships between ALA or EPA + DHA intake and respiratory symptoms among US adults with COPD, as well as variation in relationships based on personal characteristics or exposures. RESULTS: Of 878 participants, mean age was 60.6 years, 48% were current smokers, and 68% completed high school. Omega-3 intake was, 1.71 ± 0.89 g (ALA), and 0.11 ± 0.21 g (EPA + DHA). Logistic regression models, adjusting for age, gender, race, body mass index, FEV1, education, smoking status, pack-years, total caloric intake, and omega-6 (linoleic acid, LA) intake demonstrated no primary associations between omega-3 intake and respiratory symptoms. Interaction terms were used to determine potential modification of relationships by personal characteristics (race, gender, education) or exposures (LA intake, smoking status), demonstrating that at lower levels of LA intake, increasing ALA intake was associated with reduced odds of chronic cough (pint = 0.015) and wheeze (pint = 0.037). EPA + DHA, but not ALA, was associated with reduced symptoms only among current smokers who did not complete high school. CONCLUSIONS: Individual factors should be taken into consideration when studying the association of fatty acid intake on respiratory diseases, as differential responses may reveal susceptible subgroups.

Environmental exposure to endotoxin and its health outcomes: A systematic review.

Exposure to endotoxin occurs environmentally and occupationally. There are several differences between them in terms of the variety and severity of health outcomes, possible exposed groups and type and route of exposure. Occupational exposures caused adverse health outcomes in almost all cases, but there is disparity in the incidence of significant health outcomes due to environmental exposure to endotoxin. This study has therefore endeavoured to investigate health outcomes from environmental exposure to endotoxin. A systematic review was conducted of three databases and non-occupational studies reporting the environmental concentration of endotoxin, and observed health outcomes in exposed groups were included in the review (n = 27). The studies showed that first exposure to endotoxin occurs in infancy by the inhalation route. Inhalation is the only exposure route that can induce inflammation as the main symptom of exposure to endotoxin. The studies included were conducted using four approaches: molecular immunology, measurement of lung volumes, clinical sensitisation test and diagnosis of asthmatic and respiratory symptoms such as wheezing. By the immunological approach, all the included studies reported that environmental exposure to endotoxin, especially at a younger age, has a protective effect on the incidence of asthma in adolescence. The main disparity observed was in studies using the approach of diagnosed asthma. Overall, however, they confirm the protective effect of exposure to endotoxin although, in the case of children with non-atopic asthma, the results could be different.

Long term effect of sulfur mustard exposure on hematologic and respiratory status, a case control study.

The long term effect of sulfur mustard (SM) exposure including, total and differential white blood cells (WBC), hematological parameters, pulmonary function tests (PFT), and respiratory symptoms (RS) in chemical war victims (CWV) exposed to SM 27-30 years ago were examined. Forty-six CWV and 42 control subjects with similar age from the general population were studied. Hematologic parameters, RS including; chest wheezing, night cough, night wheezing and cough, wheezing due to exercise (by Persian questionnaire), and PFT were assessed in all subjects. Total WBC count (p < 0.001), hematocrit, and mean corpuscular volume (MCV) were significantly higher (p < 0.05 and 0.001, respectively) but mean corpuscular hemoglobin concentration (MCHC) and the percent of monocyte were lower in veterans than control group (p < 0.001 and 0.01, respectively). All PFT values were also lower in CWV compared to control subjects (p < 0.001 for all cases). Maximal mid expiratory flow (MMEF) and maximal expiratory flow at 75% of forced vital capacity (MEF75) were the most affected PFT values in CWV and were 50% or lower of predicted values. All CWV reported respiratory symptoms, including; chest wheezing, night cough, night wheezing and cough, and wheezing due to exercise were higher in the veterans compared to control group (p < 0.001 for all cases). Increased total WBC count and RS but reduction in monocyte, MCHC, and PFT values were shown in CWV 27-30 years after exposure to SM. These results indicated profound hematologic (mainly WBC) and pulmonary effect of SM long time after exposure.

A breath sound analysis in children with cough variant asthma.

BACKGROUND: Cough variant asthma (CVA) is characterized by a chronic cough and bronchial hyperresponsiveness without confirmation of wheezing. Using a breath sound analyzer, we evaluate the characteristics of breath sound in children with CVA. METHODS: Nine children with CVA (median age, 7.0 years) participated. The existence of breath sounds was confirmed by sound spectrogram. Breath sound parameters, the frequency limiting 50% and 99% of the power spectrum (F50 and F99), the roll-off from 600 to 1200 Hz (Slope) and spectrum curve indices, the ratio of the third and fourth area to the total area of the power spectrum (P3/PT and P4/PT) and the ratio of power and frequency at 50% and 75% of the highest frequency of the power spectrum (RPF75 and RPF50) were calculated before and after ß2 agonist inhalation. A spirogram and/or forced oscillation technique were performed in all subjects. RESULTS: On a sound spectrogram, wheezing was confirmed in seven of nine patients. All wheezing on the image was polyphonic, and they almost disappeared after ß2 agonist inhalation. An analysis of the breath sound spectrum showed that PT, P3/PT, P4/PT, RPF50 and RPF75 were significantly increased after ß2 agonist inhalation. CONCLUSIONS: Children with CVA showed a high rate of inaudible wheezing that disappeared after ß2 agonist inhalation. Changes in the spectrum curve indices also indicated the bronchial reversibility. These results may suggest the characteristics of CVA in children.

Intravenous magnesium sulfate for acute wheezing in young children: a randomised double-blind trial.

Magnesium sulfate has been shown to be an effective treatment in older children with asthma exacerbations, but it has not been investigated in acute severe virus-induced wheezing in young children.The study enrolled 61 children aged 6 months to 4 years. Inclusion criteria were severe wheezing, classified as a score of ≥6 points as assessed by the Respiratory Distress Assessment Instrument (RDAI) after initial treatment with salbutamol, and the symptoms of acute viral infection. The children were randomly allocated to receive either an infusion of magnesium sulfate (40 mg·kg-1) or 0.9% sodium chloride as a placebo infusion for 20 min. Primary outcome measure was mean change in RDAI scores from baseline to 6 h after the treatment.Change in the severity of wheezing from baseline to 6 h after the treatment, as measured by mean±sd RDAI scores, was 4.7±2.6 in the magnesium sulfate group and 4.2±4.2 in the placebo group (difference 0.5, 95% CI -1.3 to 2.3, p=0.594).Intravenous magnesium sulfate was ineffective in treating acute severe virus-induced wheezing in young children, in contrast to the previous efficacy demonstrated in older children.

The effect of montelukast on early-life wheezing: A randomized, double-blinded placebo-controlled study.

BACKGROUND: Cysteinyl-leukotrienes are increased in the airways of infants with virus-associated wheezing. We aimed to determine the effects of a cysteinyl-leukotriene-1 receptor antagonist on symptoms during an early-life wheezing illness and to investigate the factors that affect the response to this drug. METHOD: This placebo-controlled double-blinded randomized controlled trial recruited children aged 3-36 months with wheezing illness and randomized to active drug or placebo for 56 days. A symptom score diary (SSD) was kept by the children's caregivers. RESULTS: One-hundred patients completed the study, and 62 (30 montelukast and 32 placebo) were analyzed. There were no significant differences in the percent of symptom-free days, symptom scores, and the need for rescue salbutamol between the two groups. However, the percent of symptom-free days within the first week was significantly higher for the montelukast than for the placebo group (13.8 ± 4.1% vs. 5.4 ± 3.4%; P = 0.028); wheezing score at 7th day was significantly lower for the montelukast than for the placebo group (0.5 ± 0.1 vs. 1.4 ± 0.2; P = 0.002). In addition, the number of inhaled ß2 -agonist rescue episodes per day during the first week was significantly lower for the montelukast compared with the placebo group (12.7 ± 1.8 vs. 19.2 ± 1.6; P = 0.013). Conclusions Our results indicate that montelukast may be effective for reducing caregiver-observed wheezing and the need for salbutamol during the first week of treatment for early-life wheezing. The impact for caregivers and the optimal duration of treatment will need to be explored in studies of larger size.