Joseph Lipworth

Small airway dysfunction is associated with poorer asthma control

To the Editor: The clinical relevance of the small airways in persistent asthma has been gaining greater recognition in recent years [1]. Studies have shown that a significant proportion of asthmatics on standard treatment fail to achieve satisfactory asthma control. For example, in one study of 3421 asthmatic subjects who underwent guideline-driven dose titration with standard inhaled corticosteroids (ICS)/long-acting β-agonist (LABA) combination therapy over 1 year, only 41% achieved total control of their asthma while 71% were well controlled [2]. Anderson et al. [3] found a high prevalence of adult patients with persistent small airway dysfunction determined by impulse oscillometry (IOS) (assessed as the difference between the resistance at 5 Hz ( R 5) and that at 20 Hz oscillation ( R 20)) and spirometry (assessed as the forced expiratory flow at 25–75% of forced vital capacity (FEF25–75%)) across British Thoracic Society (BTS) treatment steps for asthma, many of whom had a preserved forced expiratory volume in 1 s (FEV1). This, in turn, suggests an unmet clinical need in terms of patients who may have a small airway asthma phenotype. We therefore evaluated whether small airway dysfunction was associated with worse control in adult asthmatics with a preserved FEV1 (>80% predicted). Spirometry and IOS measurements from unselected asthmatics referred from primary care who attended screening for clinical trials were linked to prescription data. The prescription data were obtained from the Tayside Health Informatics Centre (Dundee, UK), which links all community-dispensed prescriptions using a person’s unique identifier, the Community Health Index. Spirometry and IOS measurements from asthmatics were …

Utility of impulse oscillometry in patients with moderate to severe persistent asthma

Outcomes measured with impulse oscillometry are more closely related to asthma control than spirometry in moderate to severe asthma.

Influence of β2-adrenoceptor 16 genotype on propranolol-induced bronchoconstriction in patients with persistent asthma.

response to gum arabic after experiencingwork-related rhinitis and dyspnea.6 One case report involved 4 separate allergic reactions after a man drank coffee made from gum arabicecoated coffee beans.7 Two of the reactions were anaphylactic in nature, leading to cardiac arrest; however, these were noted to have occurred after the patient had been prescribed timolol eye drops. Although the patient was found to have dual sensitivity to coffee and gum arabicecoated coffee beans via skin prick testing and human basophil degranulation testing, the case also highlighted the potential risk of b-blockers in potentiating anaphylaxis to these allergens. An extensive search on cases of anaphylaxis to gum arabic alone yielded no results. We report a case of a 21-year-old college student with no prior exposure to the pharmaceutical or confectionery industry who experienced anaphylaxis after drinking soda that contained gum arabic. The patient reported having symptoms of anaphylaxis 1 hour after imbibing approximately 4 oz of Mountain Dew Code Red (contains gum arabic). She noted urticaria on the central upper part of her chest, dyspnea, and inability to complete full sentences. The patient was then immediately taken to her university’s health services clinic for further evaluation, at which time she was noted to have facial swelling and wheezing on examination. Because of the anaphylactic reaction, the patient was initially unclear of all the events that occurred before treatment; however, further investigation revealed that the patient’s clinical presentation immediately improved after epinephrine administration in the health clinic. She reported that since the incident, she has avoided drinking

Real-life effect of long-acting β2-agonist withdrawal in patients with controlled step 3 asthma

Approximately 45% of patients with asthma in the United Kingdom are receiving step 3 or higher therapy,1 most commonly inhaled corticosteroids (ICSs) and long-acting b2-agonists (LABAs). The 2016 Global Initiative for Asthma (GINA) guidelines propose a cycle of assessment, stepwise adjustment of treatment, and review of response to ascertain the lowest treatment to achieve control.2 In addition, the US Food and Drug Administration advocates stopping use of LABAs once asthma control is achieved and maintained and switching to ICS monotherapy.3 In clinical practice, it is more commonly observed that patients with asthma are stepped up to ICSs or LABAs (GINA step 3) than stepped down to ICSs alone (step 2). We hypothesize that LABA withdrawal may be safely performed in patients with controlled asthma. We therefore assessed the effect of stopping LABA treatment in patients referred from primary care for inclusion in clinical trials. The East of Scotland Research Ethics Service granted ethical approval for studies included in this analysis, and all patients provided written informed consent. We evaluated a series of 58 patients with stable, GINA step 3 asthma. At the baseline visit, current asthma therapy was recorded. Spirometry (Micromedical, Chatham, United Kingdom) and Impulse oscillometry (IOS, Jaeger Masterscreen, Hochberg, Germany) were performed according to European Respiratory Society guidelines, and exhaled nitric oxide (NIOX, Aerocrine, Morrisville, North Carolina) was recorded. IOS is an effort-independent technique performed during quiet tidal breathing to measure frequency-dependent resistance and reactance. Resistance at 5 Hz (R5) and 20 Hz (R20) is regarded as reflecting total and central airway resistance, respectively. The difference between R5 and R20 (R5 R20) is a surrogate for the resistance of peripheral airways. IOS relates more closely to asthma control than the effortdependent spirometry.4 After the screening visit, patients had their LABA treatment stopped. If they were using combination inhalers (comprising fluticasone-salmeterol, fluticasone-formoterol, budesonideformoterol, or beclomethasone-formoterol), the patient was issued an ICS alone at a beclomethasone equivalent dose. In accordance with GINA guidelines, their ICS dose was also reduced by approximately 25%. The patients then attended a 3-weeks follow-up to have tests performed again. They were issued a diary card to record their global rated symptom scores (0to 3-point scale: none, mild, moderate, severe) and reliever

β2-Adrenergic receptor Gly16Arg polymorphism and impaired asthma control in corticosteroid-treated asthmatic adults.

β2-Agonists are the most commonly prescribed asthma medication, and the β2-adrenergic receptor gene has been studied extensively. A single-nucleotide polymorphism causing the substitution of arginine (Arg) for glycine (Gly) at position 16 (Gly16Arg) of the β2-adrenergic receptor affects the response to β2-agonists. Regular exposure to β2-agonists results in down-regulation and uncoupling of β2-adrenoreceptors with associated subsensitivity or tachyphylaxis of response.1 Retrospective studies have reported an impaired therapeutic response in terms of peak expiratory flow in adults treated with long-acting β2-agonists (LABAs).

P192 A pilot study to assess the influence of β2-adrenoceptor polymorphism on small airway function and asthma control

Introduction and Objectives It is increasingly recognised that small airway dysfunction is associated with suboptimal asthma control. We have previously reported that β2-adrenoreceptor polymorphism at position 16 (i.e. Arg/Gly) is not related to FEV1 or airway hyper-responsiveness in persistent asthmatics.1 However effects of β2-adrenoreceptor polymorphism on the small airways are not known. This pilot study in a different cohort of patients evaluated the effects of β2-adrenoreceptor polymorphism on small airway function and asthma control. Impulse oscillometry (IOS) was used to assess small airway function along with FEF25–75. IOS is an effort independent test performed during normal quiet tidal breathing and is able to discriminate between changes in central and peripheral airways. Resistance at 5 Hz (R5) and 20 Hz (R20) indicate total and central airway resistance respectively - the difference between R5 and R20 indicates peripheral airway resistance. Asthma control was assessed using the Asthma Control Questionnaire (ACQ-5). Methods We collected spirometry, IOS and ACQ data from patients attending a secondary care asthma clinic. A total of 100 patients all taking inhaled corticosteroids (20% taking long acting beta-agonists) were included with a mean: age 39.2 year FEV1 88.4%, FEF25–75% 55.5%, R5%162%, R5-R20 0.07 kPa/l/s, ACQ-5 1.70 Results 48% (n = 48) had 1 or 2 copies of the Arg allele (i.e. Arg/Arg or Arg/Gly genotypes) while 52% (n = 52) had no copies of the Arg allele (i.e. Gly/Gly genotype). There was no significant difference between genotypes in terms of FEV1, FEF25–75, R5, R5-R20 or ACQ. Furthermore there was no significant effect of LABA according to Arg/Gly polymorphism. Reference 1. Manoharan A, Anderson WJ, Lipworth BJ. Influence of β2-adrenergic receptor polymorphism on methacholine hyperresponsiveness in asthmatic patients. Ann Allergy Asthma Immunol 2013;110: 161–164 Abstract P192 Table 1: Spirometry, IOS and ACQ-5 according to Arg/Gly-16 polymorphism Arg-Arg / Arg-Gly Gly-Gly p-value FEV1(% predicted) 88 (82-94) 85 (78-91) 0.46 FEF25-75(% predicted) 53 (45-62) 49 (41-57) 0.48 R5(% predicted) 149 (132-168) 178 (147-209) 0.58 R20(% predicted) 142 (127-156) 146 (130-162) 0.80 R5 – R20 (kPa/L/S) 0.07 (0.05-0.09) 0.07 (0.05-0.09) 1.00 ACQ-5 1.38 (0.92-1.84) 1.96 (1.54-2.38) 0.07