Herbal treatments of asthma: a systematic review.

BACKGROUND: Asthma is a condition, often chronic, characterized by respiratory symptoms, variable airflow limitation and/or airway hyper-reactivity with symptoms causally related to family history, environmental influences, exposure to viruses and allergens as examples. The high economic burden associated with asthma is associated primarily with health care costs, missed work or school days. This systematic review was conducted to determine the study quality of articles investigating ayurvedic/collateral herbs, the effectiveness/efficacy and safety profile, as reported in the studies. METHODS: Literature searches were conducted using PubMed, EMBASE, Mantis, Ovid, Annotated Bibliography of Indian Medicine, and Cochrane library to identify published trials on herbal medicines for asthma of which Ayruvedic herbals are a subset. Randomized Controlled Trials (RCTs) and Quasi-Experimental Designs (QEDs) were included in this systematic review. The classic Jadad Scale, Singh RCT Scale with additional domains than Jadad, Safety Scoring Scale for clinical trials and the Singh QED Scale based on expanded features of QEDs were used to assess study quality. Herbs included in Traditional Chinese Medicine were excluded from this review. Forty-two articles were retrieved and 37 studies were ultimately reviewed utilizing 3 independent evaluators/1 arbitrator. RESULTS: Articles reviewed indicated benefit from most of the herbs used either as a primary or adjunctive treatment for Asthma. Study quality was mixed and therefore caution in interpretation of findings of usefulness of these herbals must be suggested. Limited safety information was mixed and generally was related to GI symptoms, though one herbal investigated reported more serious side effects. CONCLUSIONS: Herbs may be useful in treatment of asthma. There is insufficient evidence to make recommendations for or against the use of these herbals. Established effectiveness must be balanced with study quality and safety profile for the herb.     

Inhaled fluticasone propionate and adrenal effects in adult asthma: systematic review and meta-analysis.

The dose-response relationship of inhaled fluticasone propionate (FP) for adrenal suppression in adults with asthma is not clear. The current authors carried out a systematic review and meta-analysis of placebo-controlled randomised dose-response studies of >or=4 weeks' duration, which assessed the adrenal effects of FP by cosyntropin stimulation tests in adult asthma. The main outcome measure was the proportion of subjects with adrenal function below the lower limit of the normal range. Five studies, with a total of 732 subjects with asthma, met the inclusion criteria. Data on daily doses >1,000 mug were limited to one study. The proportion of subjects with adrenal function below the lower limit of the normal range on placebo was 3.9%; for a 500-microg per day increase in FP dose the odds of an abnormality increased by 1.38 (95% confidence interval 1.01-1.59). The continuous secondary outcome measures showed an inverse linear relationship with the FP dose up to 2,000 microg.day(-1). In conclusion, for routine prescribing within the established therapeutic dose-response range (50-500 microg.day(-1)), fluticasone propionate has minimal effects on adrenal function. This conclusion is limited by the paucity of long-term studies of daily doses of fluticasone propionate >1,000 mug and by the considerable individual variability in the response.     

Dose-response relationship of inhaled budesonide in adult asthma: a meta-analysis.

The aim of this study was to examine the dose-response relationship of inhaled budesonide in adolescents and adults with asthma. A meta-analysis was carried out on placebo-controlled, randomised clinical trials, presenting data on at least one outcome measure of asthma and using at least two doses of budesonide, delivered by turbuhaler or metered-dose inhaler + spacer twice daily. A total of six studies of 1,435 adolescents and adults, with mild to moderately severe asthma, met the inclusion criteria for the meta-analysis. A negative exponential model indicated that 80% of the benefit at 1,600 micrograms.day-1 was achieved at doses of approximately 200-400 micrograms.day-1 and 90% by 300-600 micrograms.day-1. Meta-regression with a quadratic term in dose showed that the maximum effect was obtained with doses of approximately 1,000 micrograms.day-1. In conclusion, the available published data indicate that, in adolescents and adults with mild to moderate asthma, most of the therapeutic benefit of budesonide delivered by turbuhaler or metered-dose inhaler + spacer is achieved with a dose of approximately 400 micrograms.day-1 and the maximum effect is achieved at approximately 1,000 micrograms.day-1. This conclusion is qualified by the recognition that there is considerable individual variability in the response to inhaled corticosteroids and that the subjects included in this meta-analysis had predominantly mild to moderate asthma.     

Cough variant asthma: a review of the clinical literature.

Cough variant asthma is an occult form of asthma of which the only sign or symptom is chronic cough. This review examines 15 clinically oriented research articles on cough variant asthma and summarizes what is known about its frequency of occurrence, clinical presentation, diagnosis, treatment, and natural history. Cough variant asthma is a common problem among all ages that frequently goes unrecognized. Pulmonary function, as measured by spirometry, is often within normal limits. Any patient with a nonproductive, nocturnal cough lasting more than two weeks, should receive an empiric trial of bronchodilators. The natural history of cough variant asthma is variable. A significant proportion of patients followed over time develop the classic signs and symptoms of asthma, whereas for many patients, cough resolves without need for further treatment.     

Rational oral corticosteroid use in adult severe asthma: A narrative review

OCS play an important role in the management of asthma. However, steroid‐related AE are common and represent a leading cause of morbidity. Limited published studies suggest OCS usage varies across countries and recent registry data indicate that at least 25–60% of patients with severe asthma in developed countries may at some stage be prescribed OCS. Recent evidence indicate that many patients do not receive optimal therapy for asthma and are often prescribed maintenance OCS or repeated steroid bursts to treat exacerbations. Given the recent progress in adult severe asthma and new treatment options, judicious appraisal of steroid use is merited. A number of strategies and add‐on therapies are now available to treat severe asthma. These include increasing specialist referral for multidisciplinary assessments and implementing OCS‐sparing interventions, such as improving guideline adherence and add‐on tiotropium and macrolides. Biologics have recently become available for severe asthma; these agents reduce asthma exacerbations and lower OCS exposure. Further research, collaboration and consensus are necessary to develop a structured stewardship approach including realistic OCS‐weaning programmes for patients with severe asthma on regular OCS; education and public health campaigns to improve timely access to specialized severe asthma services for treatment optimization; and implementing targeted strategies to identify patients who warrant OCS use using objective biomarker‐based strategies.     

The adult incidence of asthma and respiratory symptoms by passive smoking in uterus or in childhood

The effects of pre- or postnatal passive smoking on the adult incidence of asthma have not been reported previously. Between 1985 and 1996/1997, we conducted an 11-year community cohort study on the incidence of asthma and respiratory symptoms in Western Norway. The cohort included 3,786 subjects aged 15 to 70 years, of which 2,819 were responders at both baseline and follow-up. The incidence of asthma and five respiratory symptoms by self-reported exposure to maternal smoking in utero and in childhood, as well as smoking by other household members in childhood, was examined. After adjustment for sex, age, education, hay fever, personal smoking, and occupational exposure, maternal smoking was associated with asthma, phlegm cough, chronic cough, dyspnea grade 2, attacks of dyspnea, and wheezing, with odds ratios (95% confidence intervals [CI]) of 3.0 (1.6, 5.6), 1.7 (1.1, 2.6), 1.9 (1.2, 3.0), 1.9 (1.2, 3.0), 2.0 (1.3, 3.0), and 1.4 (0.9, 2.2), respectively. The adjusted attributable fractions (95% CI) of the adult incidence of asthma were 17.3% (5.2, 27.9) caused by maternal smoking and 9.3% (95% CI, -23.2, 33.2) caused by smoking by other household members. Exposure to pre- and postnatal smoking carries a substantial risk for developing adult asthma and respiratory symptoms.     

Recurrent pneumonia: a review of 90 adult patients.

Recurrent pneumonia is still an important problem. In this retrospective study we reviewed the records of 90 patients with a history of 3 or more episodes of acute pneumonia. The 90 patients accounted for altogether 347 episodes of acute pneumonia, treated at the Department of Infectious Diseases, Lund. 12 patients died while being treated for pneumonia at the department. Pneumonia alone caused the death in 7 of these 12 patients. In all, 51 of the patients died during the 11-year study period. Death certificates, stating the cause of death, were available in 38 cases, and pneumonia was the direct cause of death in 15 patients. Most of the infections were community-acquired, only 47 were nosocomial, 20/90 patients suffered from disorders associated with immune deficiency, and 70 patients had other predisposing illnesses. We found a larger number of underlying immunoglobulin deficiencies (11 patients of 38 investigated) than previously reported. Of 13 patients without other known, predisposing conditions, hypogammaglobulinemia was found in 3 patients. We suggest that patients with recurrent pneumonia should be thoroughly investigated, in order to find previously unrecognized immune deficiency.     

The incidence of asthma in young adults

STUDY OBJECTIVES: Longitudinal data on adult asthma are sparse. The objectives of this study were to determine the incidence of asthma and to establish the risk factors for the development of asthma in subjects who were 12 to 41 years old over an 8-year period. DESIGN: From birth cohorts over the period 1953 to 1982 in The Danish Twin Registry, 19,349 subjects with no history of asthma, as determined by a questionnaire-based survey in 1994, answered a follow-up questionnaire in 2002. The subjects were regarded as incident asthma cases when answering "yes" to the question "Do you have, or have you ever had asthma?" in 2002, and "no" to the same question in 1994. RESULTS: A total of 838 cases (4.3%) of new asthma were identified in 2002. The incidence rates of asthma were 4.5 and 6.4 per 1,000 person-years, respectively, among male and female subjects. For all ages, the probability of adult-onset asthma was greater for female subjects (odds ratio [OR], 1.49; p < 0.001), and for both sexes there was a slow decline in probability with increasing age. There was a positive association between increasing body mass index (BMI) and risk of adult-onset asthma applying to both sexes (OR, 1.05 per unit; p < 0.001). Furthermore, positive associations were found between incident asthma and a history of hay fever (OR: male subjects, 4.2; female subjects, 3.7; p < 0.001), eczema (OR: male subjects, 3.5; female subjects, 2.0; p < 0.001), and both (OR: male subjects, 6.9; female subjects, 8.0; p < 0.001). CONCLUSIONS: There is a continuing high incidence of asthma past childhood that is most pronounced among female subjects. Increasing levels of BMI are associated with a greater likelihood of developing asthma for both sexes. A substantial portion of cases of adult asthma is preceded by upper airway allergic symptoms and/or eczema, thus indicating a shared pathogenesis.     

Omalizumab (Xolair) improves quality of life in adult patients with allergic asthma: a review

Physicians are increasingly aware that asthma causes significant impairment of the patients physical, psychological, and social well-being. Whilst standard clinical endpoints provide significant information on airway status during treatment, it is important to determine whether such improvements overcome the functional impairment that patients have to deal with on a daily basis. As such, assessment of health-related quality of life (QoL) is an important aspect of asthma management in clinical practice. Omalizumab (Xolair) is a recombinant humanized monoclonal anti-immunoglobulin E (IgE) antibody that represents a new therapeutic approach to IgE-mediated diseases such as allergic asthma. Clinical studies show that omalizumab improves the control of allergic asthma whilst reducing steroid consumption, and enhances long-term disease control in patients with recurrent symptoms. Using established and validated QoL methodology, two placebo-controlled clinical studies in adults with moderate-to-severe allergic asthma have shown that patients treated with omalizumab experience a clinically relevant improvement in all aspects of their asthma-related QoL, changes that were significantly superior to those observed for placebo. Such improvements were apparent when omalizumab was added to existing therapy with inhaled corticosteroids, and maintained during a subsequent steroid-reduction phase. Through effective disease control, omalizumab therefore leads to significant improvements in health-related QoL that are meaningful to patients with allergic asthma.     

Nitric oxide and asthma: a review

Nitric oxide (NO) is synthesized from the amino acid arginine by enzymes called nitric oxide synthases. NO has an important physiologic role in the regulation of vascular tone, response to vascular injury, and hemostasis. It also acts as a neurotransmitter for the nonadrenergic noncholinergic nerves and has important antimicrobial, immunologic, and proinflammatory activities. The lung is rich in nitric oxide synthases, and NO is normally present in the exhaled air. Use of NO in the treatment of asthma has not withstood the test of time and is not recommended. With the advent of analyzers capable of measuring NO rapidly and reliably, however, the analysis of NO in exhaled air is being increasingly recognized as a potential noninvasive test for the evaluation of the inflammatory component of the pathology of patients with asthma. An increase in the exhaled NO has been shown to accompany eosinophilic inflammation and to correlate with other indices of inflammation in asthma. Exhaled NO increases during exacerbation and decreases with recovery in patients with asthma. As exhaled NO is not increased during bronchospasm in the absence of coexisting inflammation, it could serve to differentiate between the inflammatory and bronchospastic components in asthma, thereby guiding therapy with steroids and other anti-inflammatory medications. Levels of NO also can be increased in certain other conditions, for example, allergic rhinitis and adult respiratory distress syndrome, but these can be clinically differentiated from asthma and do not lessen the diagnostic value of exhaled NO. Measurements of exhaled NO are influenced by several physiologic and technical variables, which results in a wide variation in the levels reported from the different laboratories. Standardization of technique, a better understanding of the confounding effects of physiologic and environmental variables, and establishment of the normal range and variability of exhaled NO are needed before its measurement could gain wide acceptance as a clinically useful test. Development of less expensive NO analyzers is also an important consideration.     

Continuous vs intermittent beta-agonists in the treatment of acute adult asthma: a systematic review with meta-analysis

BACKGROUND: Since the late 1980s, there has been considerable clinical and academic interest in the use of continuous aerosolized bronchodilators for the treatment of patients with acute asthma. These studies have suggested that this therapy is safe, is at least as effective as intermittent nebulization, and may be superior to intermittent nebulization in patients with the most severely impaired pulmonary function. OBJECTIVES: To determine whether continuous nebulization offered an advantage over intermittent nebulization for the treatment of adults with acute asthma in the emergency department (ED). DESIGN: Systematic review of randomized controlled trials of adults with acute asthma. OUTCOMES: Change in pulmonary function tests as primary outcome, and admissions to the hospital and side effects as secondary outcomes. RESULTS: Six studies including 393 adults with acute asthma were selected. No significant differences were demonstrated between the two delivery methods in terms of pulmonary function measures obtained after 1 h of treatment (standardized mean difference [SMD], -0.15; 95% confidence interval [CI], -0.35 to 0.05) and after 2 to 3 h of treatment (SMD, -0.19; 95% CI, -0.39 to 0.01). No significant heterogeneity was demonstrated (p > 0.5). At the end of treatment, there was a significantly greater decrease in pulse rate when the continuous nebulizer was used (weighted mean difference [WMD], -6.82; 95% CI, -8.67 to -3.90 beats/min; chi(2), 2.55; degrees of freedom [df], 4; p = 0.6). Additionally, the analysis showed a significant decrease of serum potassium concentration with the use of intermittent nebulization (WMD, 0.12; 95% CI, 0.24 to 0.01 mmol/L; chi(2), 0.5; df, 2; p = 0.8). However, this finding was obtained on the analysis of only two trials. Finally, at the end of the study period, no significant differences were identified between patients treated with continuous or intermittent nebulization with respect to hospital admission (relative risk, 0.68; 95% CI, 0.33 to 1.38; chi(2), 2.06; df, 1; p = 0.2). CONCLUSIONS: Overall, this review supports the equivalence of continuous and intermittent albuterol nebulization in the treatment of acute adult asthma.     

Acute asthma in adults: a review

All patients with asthma are at risk of having exacerbations. Hospitalizations and emergency department (ED) visits account for a large proportion of the health-care cost burden of asthma, and avoidance or proper management of acute asthma (AA) episodes represent an area with the potential for large reductions in health-care costs. The severity of exacerbations may range from mild to life threatening, and mortality is most often associated with failure to appreciate the severity of the exacerbation, resulting in inadequate emergency treatment and delay in referring to hospital. This review describes the epidemiology, costs, pathophysiology, mortality, and management of adult AA in the ED and in the ICU.     

Mucociliary clearance in adult asthma.

Severe impairment of mucociliary clearance (MC) in hospitalized asthmatics has recently been demonstrated in peripheral and central airways. MC was also shown to improve with clinical recovery and hospital discharge (2). In the present study, we measure MC in chronic, stable asthma in subjects with a wide range of obstruction to see if MC was related to the severity of chronic disease. We separated the subjects into those with severe obstruction with expiratory flow limitation during tidal breathing (FL subjects) and those without tidal flow limitation (NFL subjects) to see if the presence of chronic flow limitation was associated with regional MC abnormalities. Seventeen asthmatic patients were studied. Mucociliary clearance was assessed using inhaled radioaerosol and serial measurements of the retention of radioactivity over 2 h. By controlling breathing pattern, the initial pattern of deposition in the lungs was matched, with all subjects having a predominance of particles in the central airways. This pattern was normalized for regional lung volume using a xenon equilibrium scan and expressed as a specific central to peripheral (sC/P) ratio. The percentage retention of deposited radioactivity at 120 min ranged from 19 to 83% (mean, 52%). FL subjects had a mean retention at 120 min of 66% (range, 55 to 83%). The NFL subjects had a mean retention at 120 min of 33% (range, 19 to 51%). Throughout the 2-h study period, retention by the FL group was significantly greater than that of the NFL group with separation of 95% confidence intervals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cost-effectiveness of asthma therapy: a comprehensive review

Background: Asthma has an important impact in terms of both direct and indirect costs. In Europe, the disease costs €?19?000 million a year. Moreover, the cost is greater among patients with severe uncontrolled asthma and is even higher when the work productivity is also taken into account. Improved control of the disease results in cost savings. In this context, cost-effectiveness and cost-utility studies offer important information for clinicians in deciding the best treatment options for asthmatic patients and contribute to ensure an efficient use of the available healthcare resources. Methods: An English and Spanish literature search using electronic search engines (PubMed and EMBASE) was conducted in peer-review journals, from 2009 to June 2014. In order to perform the search for the most suitable and representative articles, key words were selected (“asthma”, “cost-effectiveness”, “cost-utility”, “QALY”, “cost-benefit”, “economic impact of asthma” “healthcare cost”, “asthma treatment” and “work productivity with asthma”). Results: Two-hundred forty-three titles and abstracts were identified by the primary literature search. The full text of the potentially 76 eligible papers was reviewed, and 22 articles were qualified to be finally included. Conclusions: This article provides a comprehensive review on the evidence of cost-effectiveness of asthma treatments derived from the published literature and offers an overall summary of the socioeconomic burden of asthma and its relationship with the degree of disease control. Management alternatives, such as the use of combination therapy with ICS/LABA or omalizumab, when administered according to their current therapeutic indications, have been shown to be cost-effective.     

The incidence of sexually acquired reactive arthritis: a systematic literature review

Reactive arthritis (ReA) is an inflammatory spondyloarthritis occurring after infection at a distant site. Chlamydia trachomatis is proposed to be the most common cause of ReA, yet the incidence of sexually acquired ReA (SARA) has not been well established. We therefore carried out a systematic literature review to collate and critically evaluate the published evidence regarding the incidence of SARA. MEDLINE and EMBASE databases were searched using free-text and MeSH terms relating to infection and ReA. The title and abstract of articles returned were screened independently by two reviewers and potentially relevant articles assessed in full. Data was extracted from relevant articles and a risk of bias assessment carried out using a validated tool. Heterogeneity of study methodology and results precluded meta-analysis. The search yielded a total of 11,680 articles, and a further 17 were identified from review articles. After screening, 55 papers were assessed in full, from which 3 met the relevant inclusion criteria for the review. The studies reported an incidence of SARA of 3.0–8.1 % and were found to be of low to moderate quality. More studies are required to address the lack of data regarding the incidence of SARA. Specific and sensitive classification criteria must be developed in order for consistent classification and valid conclusions to be drawn. In clinical practice, it is recommended clinicians discuss the possibility of ReA developing at the time of STI diagnosis and to encourage patients to return if they experience any relevant symptoms.     

Occupational asthma in the developing and industrialised world: a review.

Occupational asthma is the most common occupational lung disease in industrialised countries, and the second most common occupational lung disease reported after pneumoconioses in developing countries. The median proportion of adult cases of asthma attributable to occupational exposure is between 10% and 15%. The population attributable fraction appears to be similar in industrialised and developing countries characterised by rapid industrialisation (13-15%), but lower in less industrialised developing countries (6%). The high-risk occupations and industries associated with the development of occupational asthma vary depending on the dominant industrial sectors in a particular country. High-risk exposure to cleaning agents and pesticide exposure in developing countries appear to be as important as exposure to isocyanates, cereal flour/grain dust, welding fumes, wood dust and, more recently, hairdressing chemicals, commonly reported in industrialised countries. The reported mean annual incidence of occupational asthma in developing countries is less than 2 per 100 000 population, compared to very high rates of up to 18/100 000 in Scandinavian countries. While occupational asthma remains under-recognised, especially in developing countries, it remains poorly diagnosed and managed and inadequately compensated worldwide. Primary and secondary preventive strategies should be directed at controlling workplace exposures, accompanied by intense educational and managerial improvements. Appropriate treatment remains early removal from exposure to ensure that the worker has no further exposure to the causal agent, with preservation of income. However, up to one third of workers with occupational asthma continue to remain exposed to the causative agent or suffer prolonged work disruption, discrimination and risk of unemployment.