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The future of combining inhaled drugs for COPD.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality globally, and its prevalence is projected to continue to increase owing to trends in smoking. Treatment of COPD has evolved from the initial adaptations of drugs and treatment strategies successfully used in asthma into more specific pharmacological strategies following global guidelines.

Bronchodilating anticholinergic and beta-2-stimulating agents and anti-inflammatory corticosteroid drugs delivered by inhalators are the mainstay of COPD treatment. Despite significant progress, current pharmacotherapies neither fully alleviate the airway obstruction in COPD, nor reverse the progressive nature of the disease. This review discusses inhalation therapies which have recently become clinically available or are being developed, with focus on combination therapies. There is accumulating evidence that the combination of two or all three drug classes, triple therapy, is superior to single drug therapy.

Several fixed combinations of both currently available and novel molecules will be launched for clinical use within the next few years. Also, improved understanding of subgroups within the clinical spectrum of COPD, is likely to offer new potentials to improve COPD care.

Diagnosis of Occupational Asthma: An Update.

Work-related asthma (WRA) includes patients with sensitizer- and/or irritant-induced asthma in the workplace, as well as patients with preexisting asthma that is worsened by work factors. WRA is underdiagnosed; thus, the diagnosis is critical to prevent disease progression and its potential for morbidity and mortality.

The interview is the first diagnostic tool to be used by physicians, and the question, "Does asthma improve away from work?" is of the highest sensitivity. However, history can show numerous false positives, and the relationships between asthma worsening and work should be confirmed by objective methods such as peak expiratory flow (PEF) at and away from work. PEF sensitivity and specificity can be enhanced in combination with nonspecific bronchial hyperresponsiveness to histamine/methacholine (NSBP) before and after 2 weeks at work and a similar period off work. Immunologic testing, especially skin prick test (SPT) or specific IgE, is useful for high molecular weight allergens and some low molecular weight agents. Other immunologic tests, as well as induced sputum, measurement of exhaled nitric oxide, exhaled breath condensate, and specific inhalation challenge (SIC) are methods that contribute to the diagnosis and are typically performed at specialized facilities.

A diagnosis of occupational asthma (OA) should no longer be based on a compatible history only but should be confirmed by means of objective testing. SIC is the diagnostic gold standard. When SIC is not available, the combination of PEF measurement, NSBP test , a specific SPT, or specific IgE may be an appropriate alternative in diagnosing OA.

Anaphylaxis: current state of knowledge for the modern physician.

Anaphylaxis is a severe, potentially fatal, hypersensitivity reaction of rapid onset. It may trigger life-threatening cardiopulmonary compromise, often with skin and mucosal changes such as urticaria and angioedema.

The prevalence of anaphylaxis is increasing and the number of cases of fatal anaphylaxis appears to be rising. Food, insect stings, and drugs are the most common triggers. Novel triggers are increasingly seen and include delayed anaphylaxis to red meat, food-dependent exercise-induced reactions and anaphylaxis to monoclonal antibodies.

Anaphylaxis is usually IgE mediated, but other mechanisms also play a role for example direct mast cells activation. Differential diagnosis is discussed including asthma, syncope and shock; excessive endogenous histamine, food related syndromes, and some rare diagnoses. Intramuscular epinephrine is first line treatment. The role of other drugs is reviewed. Timed and serial serum tryptase measurements help to confirm the diagnosis. Long-term management is necessary to minimise the risk of recurrence and includes identification of the trigger(s), management of risk factors, education on avoidance and a formalised treatment plan with an epinephrine auto-injector if appropriate. Every patient who has experienced anaphylaxis should be referred to an allergy clinic for appropriate management. This is endorsed by many national guidelines (eg, UK NICE). Anaphylaxis is often misdiagnosed or miscoded as, for example, asthma or food allergy.

Most doctors will encounter a patient with anaphylaxis in their career and should to be familiar with the clinical features, management and mechanisms of this potentially fatal condition.

Validity and Reproducibility of the Asthma Core International Study of Asthma and Allergies in Childhood (ISAAC) Written Questionnaire Obtained by Telephone Survey.

Objective. To assess the reproducibility and validity of the International Study of Asthma and Allergies in Childhood (ISAAC) asthma written questionnaire (IAWQ) for 6- to 7-year-old children administered to their parents/caregivers through a telephone interview.

Methods. Our study included 100 children selected from three health units in Rio de Janeiro, Brazil. In total, 50 asthmatic and 50 non-asthmatic children were evaluated; all participants were required to own a household telephone line. Initially, telephone interviews were conducted with the parents/caregivers using the IAWQ. After 2 weeks, parents/caregivers were invited to complete the IAWQ under supervision provided by the researchers. After fifteen days, the telephone interviews were repeated. The reproducibility between the two telephone interviews was assessed using kappa (κ) coefficients; the construct validity was assessed by comparing the answers obtained in the initial telephone interview in both groups according to the clinical diagnosis of asthma performed by a specialist using sensitivity and specificity coefficients.

Results. Overall, data from 75 children (39 asthmatics) were analyzed, as 25 patients were excluded from the study (11 did not answer phone calls and the responding parents/caregivers for 14 patients were not the same in all study phases). Perfect agreement was observed for the indicator "wheezing in the last 12 months" (κ = 1), while substantial agreement was observed for the "wheezing with exercise," "speech limited by wheezing," and "asthma ever" indicators (κ range, 0.7-0.8). The sensitivity and specificity for "wheezing within the last 12 months" were 64.1% (95% confidence interval (CI), 47.2-78.8) and 88.9% (95% CI, 73.9-96.9), respectively. For the "asthma ever" indicator, the sensitivity and specificity were 87.2% (95% CI, 77.6-95.7) and 100% (95% CI, 90.3-1), respectively. Questionnaire specificity was high for all asthma severity indicators.

Conclusions. The IAWQ for children aged 6-7 years adapted for telephone interviews showed good reproducibility and adequate validity with an ability to distinguish between asthmatic and non-asthmatic participants. Thus, this method could be utilized in epidemiological studies on childhood asthma in locations where telephone lines are available.

Effects of the tulobuterol patch on the treatment of acute asthma exacerbations in young children.

The tulobuterol patch (TP) is a beta2-adrenergic agonist with a favorable pharmacokinetic profile used for asthma management in Japan. Because it contains tulobuterol in a molecular, crystallized form that is gradually absorbed percutaneously, TP exerts a prolonged bronchodilator effect exceeding 24 hours. Although it is a well-established treatment for asthma and wheezing, few studies have investigated whether it can reduce or prevent the symptoms associated with upper respiratory tract infections (URTIs) in young children.

This study evaluated the effect of TP on the long-term management of asthma in young children. In this 1-year, randomized, multicenter, double-blind,placebo-controlled study, children aged 0.5-3 years old with mild-to-moderate persistent asthmawere treated with either TP or placebo patch.The parents/guardians applied the TP or placebo patch to their children after URTI symptoms appeared. Respiratory symptoms were recorded daily during the 1-year observation period. Overall, 86 patients were enrolled and 80 were treated and analyzed in this study. Allpatients had been treated with anti-inflammatory drugs before enrollment. The time to symptom resolution was significantly shorter (p = 0.001) and the total respiratory symptom score (p = 0.0457) was significantly lower in the TP group than in the placebo group.

In young children with mild-to-moderate asthmawho had been treated with anti-inflammatory drugs, using the TP soon after the appearance of URTIsymptoms led to quicker resolution of respiratory symptoms and lower respiratory symptom scores.

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