Impact of changes to reimbursement of fixed combinations of inhaled corticosteroids and long-acting ß2 -agonists in obstructive lung diseases: a population-based, observational study.

BACKGROUND: In 2010, the Icelandic government introduced a new cost-saving policy that limited reimbursement of fixed inhaled corticosteroid/long-acting ß2 -agonist (ICS/LABA) combinations. METHODS: This population-based, retrospective, observational study assessed the effects of this policy change by linking specialist/primary care medical records with data from the Icelandic Pharmaceutical Database. The policy change took effect on 1 January 2010 (index date); data for the year preceding and following this date were analysed in 8241 patients with controlled/partly controlled asthma and/or chronic obstructive pulmonary disease (COPD) who had been dispensed an ICS/LABA during 2009. Oral corticosteroid (OCS) and short-acting ß2 -agonist (SABA) use, and healthcare visits, were assessed pre- and post-index. RESULTS: The ICS/LABA reimbursement policy change led to 47.8% fewer fixed ICS/LABA combinations being dispensed during the post-index period among patients whose asthma and/or COPD was controlled/partly controlled during the pre-index period. Fewer ICS monocomponents were also dispensed. A total of 48.6% of patients were no longer receiving any respiratory medications after the policy change. This was associated with reduced disease control, as demonstrated by more healthcare visits (44.0%), and more OCS (76.3%) and SABA (51.2%) dispensations. CONCLUSIONS: Overall, these findings demonstrate that changes in healthcare policy and medication reimbursement can directly impact medication use and, consequently, clinical outcomes and should, therefore, be made cautiously.

Potential negative consequences of non-consented switch of inhaled medications and devices in asthma patients.

BACKGROUND: Asthma requires individually tailored and careful management to control and prevent symptoms and exacerbations. Selection of the most appropriate treatment is dependent on both the choice of drugs and inhaler device; however, financial pressures may result in patients being switched to alternative medications and devices in an attempt to reduce costs. AIM: This review aimed to examine the published literature in order to ascertain whether switching a patient's asthma medications or device negatively impacts clinical and economic outcomes. MATERIALS AND METHODS: A literature search of MEDLINE (2001-13 September 2011) was conducted to identify English-language articles focused on the direct impact of switching medications and inhaler devices and switching from fixed-dose combination to monocomponent therapy via separate inhalers in patients with asthma; the indirect impacts of switching were also assessed. RESULTS: Evidence showed that non-consented switching of medications and inhalers in patients with asthma can be associated with a range of negative outcomes, at both individual and organisational levels. Factors that reduce adherence may lead to compromised symptom control resulting in increased healthcare resource utilisation and poorer patient quality of life. DISCUSSION: The consequences of a non-consented switch should be weighed carefully against arguments supporting an inhaler switch without the patient's consent for non-medical/budgetary reasons, such as potential reductions in initial acquisition costs, which may be associated with subsequent additional healthcare needs. CONCLUSION: Given the increasing pressure for reduced costs and efficient allocation of limited healthcare resources, an additional investment in ensuring high medication adherence may lead to greater savings due to a potentially decreased demand for healthcare services. In contrast, savings achieved in acquisition costs may result in a greater net loss due to increased healthcare consumption caused by decreased asthma control.

Contribution of ADAM33 polymorphisms to the population risk of asthma.

BACKGROUND: ADAM 33 is the first gene identified as a candidate for asthma by positional cloning techniques, with association studies reaching impressive statistical significance. It has a postulated role in myogenesis, airway modelling, and signalling via protein shedding. Concerns over the methodology of the initial study have led to several attempts at replication, with inconsistent results. METHOD: To clarify the role of ADAM33 in determining the risk of asthma in the general population, new transmission disequilibrium and case-control studies were undertaken followed by a meta-analysis of all existing data. RESULTS: Studies in Icelandic and UK populations revealed no association when taken in isolation. The meta-analysis, however, showed that the F+1 and ST+7 variants were significantly associated with asthma in both types of study. CONCLUSIONS: The additional risk imparted by this variation would account for 50,000 excess asthma cases in the UK alone. This study also demonstrates the size of study required to investigate such hypotheses adequately.

Obesity and nocturnal gastro-oesophageal reflux are related to onset of asthma and respiratory symptoms.

Several studies have identified obesity as a risk factor for asthma in both children and adults. An increased prevalence of asthma in subjects with gastro-oesophageal reflux (GOR) and obstructive sleep apnoea syndrome has also been reported. The aim of this investigation was to study obesity, nocturnal GOR and snoring as independent risk factors for onset of asthma and respiratory symptoms in a Nordic population. In a 5-10 yr follow-up study of the European Community Respiratory Health Survey in Iceland, Norway, Denmark, Sweden and Estonia, a postal questionnaire was sent to previous respondents. A total of 16,191 participants responded to the questionnaire. Reported onset of asthma, wheeze and night-time symptoms as well as nocturnal GOR and habitual snoring increased in prevalence along with the increase in body mass index (BMI). After adjusting for nocturnal GOR, habitual snoring and other confounders, obesity (BMI >30) remained significantly related to the onset of asthma, wheeze and night-time symptoms. Nocturnal GOR was independently related to the onset of asthma and in addition, both nocturnal GOR and habitual snoring were independently related to onset of wheeze and night-time symptoms. This study adds evidence to an independent relationship between obesity, nocturnal gastro-oesophageal reflux and habitual snoring and the onset of asthma and respiratory symptoms in adults.

Sensitization to house dust mites in Reykjavik, Iceland, in the absence of domestic exposure to mites.

BACKGROUND: House dust mites are common sources of indoor allergens. In Reykjavik, Iceland, 9% of the young adult population had serum-specific IgE to Dermatophagoides pteronyssinus. Sensitization to mites is usually assumed to be due to exposure to house dust mites in the indoor environment. This investigation was carried out to measure the concentrations of house dust mite allergens and to investigate which species of mites were present in beds in Iceland. METHODS: A total of 197 randomly selected adults were visited at home using the European Community Respiratory Health Survey (ECRHS) II Indoor protocol. Dust samples were collected from mattresses for measurement of house dust mite allergen concentrations and to estimate the number and type of house dust mites. Additional samples from mattresses and floors were collected from the homes of 10 patients with positive skin prick tests (SPT) to D. pteronyssinus. House dust mite allergen concentrations were measured using ELISA and examination of mite species was carried out using microscopy. Climatic parameters were assessed using psychrometer readings in the bedrooms and outdoors. RESULTS: We found two single mite specimens, both D. pteronyssinus, in two dust samples. Mite allergen analyses indicated that two other dust samples had Der f 1 results close to the cut-off of 0.1 microg/g of dust. No samples were positive for Der p 1. In an additional collection of dust from the homes of 10 SPT-positive patients no Dermatophagoides spp. were found. CONCLUSIONS: Reykjavik citizens are exposed to extremely low amounts of house dust mite allergens in their homes. Possible alternative sources for sensitization are discussed, such as bird nests, exposure from travelling abroad, or other mites or invertebrates that cross-react with house dust mite allergens. Our findings suggest that exposures other than to house dust mites indoors are possible sources of mite allergen exposure.

Allelic frequencies and patterns of single-nucleotide polymorphisms in candidate genes for asthma and atopy in Iceland.

Numerous asthma and atopy loci have been reported in studies demonstrating associations of the asthma-related phenotypes atopy, elevated IgE levels, and bronchial hyperresponsiveness with alleles of microsatellite markers and single-nucleotide polymorphisms (SNPs) within specific cytokine/chemokine and IgE-regulating genes. Although the studies reporting these observations are compelling, most of them lack statistical power. We assessed the nature, pattern, and frequency of SNPs in 24 candidate genes in Iceland and looked for associations with asthma and atopy. We identified 42 SNPs with an average minor allele frequency of 20.3% (asthma) and 20.7% (control). Twenty SNPs (48%) were within coding sequences and 90% of those led to a predicted change in protein sequence. No differences were detected in the allelic frequencies of SNPs in any of these candidate genes between control subjects and the patients with atopic asthma. Moreover, linkage analysis that included 269 patients with atopic asthma uncovered no evidence of linkage to markers associated with these genes. We conclude that this study has failed to produce evidence in support of the notion that variations within these 24 candidate atopy and asthma genes significantly influence the expression of the atopic asthmatic phenotype or contribute to the susceptibility of atopic asthma.

Exercise-induced laryngochalasia: an imitator of exercise-induced bronchospasm.

BACKGROUND: Patients with exercise-induced laryngochalasia present with dyspnea and stridor during exercise. Symptoms are due to a subtotal occlusion of the larynx resulting from mucosal edema from the aryepiglottic folds being drawn into the endolarynx. METHODS: We report on three patients with exercise-induced bronchospasm, refractory to standard therapy. RESULTS: Spirometry with flow-volume loops revealed truncation of the inspiratory limb. Abnormal movement of the arytenoid region was visualized on laryngoscopy. A diagnosis of exercise-induced laryngochalasia was made. CONCLUSIONS: Evaluation of laryngeal motion in patients with refractory exercise-induced bronchospasm is important. Surgical correction with laser laryngoplasty is effective in carefully selected cases.

Asthma: an inflammatory mediator soup.

Reversible or partially reversible airway obstruction, inflammation, and bronchial hyperresponsiveness to various stimuli are the defining characteristics of asthma. Airway obstruction in asthma is a complex event that is due to bronchospasm, inflammation, and mucus formation. Inflammation has assumed a more central role in the pathogenesis of the disease, as it contributes not only to airflow obstruction, but also to bronchial hyperresponsiveness. The inciting trigger, or inhaled allergen, in asthma induces the activation of mast cells and macrophages with the subsequent release of several proinflammatory mediators, including leukotrienes, chemotactic factors, and cytokines. Antigen processed by macrophages is presented to undifferentiated T helper cells, inducing differentiation to the Th2 phenotype, with the subsequent release of IL-4 and IL-5, causing IgE synthesis and eosinophil infiltration, respectively. Macrophage-derived cytokines, such as IL-1, TNF-alpha, and IFN-gamma, activate endothelial cells, upregulating the expression of adhesion molecules such as ICAM-1 and VCAM-1, which permit egression of leukocytes from the vasculature to the airway mucosa. Several inflammatory cells, such as eosinophils, mast cells, and macrophages, not only cause airway damage, but also synthesize cytokines that perpetuate the inflammatory process. This complex interplay of inflammatory cells and mediators causes the classic histopathophysiologic features in the airways of both symptomatic and asymptomatic individuals with asthma, emphasizing the importance of early recognition and antiinflammatory treatment.

The effects of fluoxetine combined with nicotine inhalers in smoking cessation--a randomized trial.

AIMS: Nicotine replacement therapy (NRT) is an established aid in stopping smoking, while the role of antidepressants remains uncertain. Antidepressants added to NRT might improve abstinence rates. Our aim was to determine the efficacy of nicotine inhaler and fluoxetine vs. nicotine inhaler and placebo in attempts to quit smoking. DESIGN: A randomized, double-blind, placebo-controlled trial. SETTING: A smoker's cessation clinic. PARTICIPANTS: One hundred volunteers smoking 10 cigarettes/day or more. INTERVENTIONS: Subjects were instructed to start taking a daily dose of 10 mg of fluoxetine or placebo 16 days before stopping smoking, then 20 mg 10 days before quitting, continuing for up to at least 3 months. Subjects were instructed to use 6-12 units per day of nicotine inhalers after stopping smoking for up to 6 months. MEASUREMENTS: Continuous abstinence rates recorded at various time points up to 12 months from the quit date. FINDINGS: The sustained abstinence rate for the inhaler-fluoxetine group was 54%, 40%, 29% and 21% after 1.5, 3, 6 and 12 months, respectively, compared to 48%, 40%, 32% and 23% for the inhaler-placebo group. The differences were not significant at any time point. Abstinence up to 3 months was more likely in older smokers, those with a lower Beck Depression Inventory Score (BDI), lower Fagerström Test of Nicotine Dependence (FTND) score and no history of alcoholism. Fluoxetine appeared to increase abstinence rates among high BDI smokers compared to high BDI smokers assigned placebo. Serum levels of nicotine during treatment in the inhaler-fluoxetine group were lower than in the inhaler-placebo group so that fluoxetine may have reduced inhaler use through a common site of action. CONCLUSIONS: We found no evidence that fluoxetine treatment when used as an adjunct to NRT in unselected smokers is effective, but there may be an advantage to using it in depressed smokers.

[Latex allergy - an emerging health care problem.].

Since immediate hypersensitivity reaction to natural rubber was described 17 years ago, the incidence of latex allergy has been increasing rapidly. This is in part due to a growing awareness of the problem along with improved diagnostic methods. Additionally, in accordance with universal health care plans and the HIV epidemic, more rubber products such as latex gloves and condoms are in general use. Changes in methods of rubber production may also contribute to the increasing prevalence in latex allergy. Individuals at greatest risk for developing latex allergy are patients who have undergone multiple operations. These include children with myelomeningocele (spina bifida) and congenital defects of the urinary tract. Another high risk group includes health care providers and individuals working in rubber production. Latex containing products are in general use in the hospital setting as well as in the home environment. They can therefore pose a great risk to sensitized patients if prophylactic measures are not undertaken. Defining high risk patients and subsequent diagnosis with appropriate skin tests are important. Patients with latex allergy must then be provided with self-administered adrenalin (Epi-pen) and instructed in avoidance measures. In this article we describe 23 individuals who have been diagnosed allergic to latex in Iceland.

Respiratory infections and asthma.

Airway responsiveness is increased during respiratory virus infections, both in subjects with asthma and without underlying pulmonary disease. Furthermore, the airway hyperresponsiveness is altered for a prolonged period of time, weeks or months after the viral illness has subsided. This article reviews the possible mechanisms of virus-associated airway hyperresponsiveness, including the complex interplay of IgE-dependent reactions, changes in autonomic nervous system function and inflammation, epithelial damage, effects of viruses on the cellular immune response, and enhanced late-phase response.

Cutis marmorata telangiectatica congenita with terminal transverse limb defects.

We describe a girl with clinical and histopathological manifestations characteristic of Cutis Marmorata Telangiectatica Congenita (CMTC) associated with Terminal Transverse Limb Defects (TTLD). In contrast to previous reports on this rare syndrome, no cutaneous atrophy or aplasia was evident in our patient.