Naghmeh Radhakrishna

Comorbidities in difficult asthma are independent risk factors for frequent exacerbations, poor control and diminished quality of life

Little is known about how comorbidities affect difficult asthma patients across different domains of asthma outcomes. We hypothesized that comorbidities in difficult asthma significantly influence asthma outcomes.

Validated questionnaires heighten detection of difficult asthma comorbidities

ABSTRACT Objective: Multiple extra-pulmonary comorbidities contribute to difficult asthma, but their diagnosis can be challenging and time consuming. Previous data on comorbidity detection have focused on clinical assessment, which may miss certain conditions. We aimed to locate relevant validated screening questionnaires to identify extra-pulmonary comorbidities that contribute to difficult asthma, and evaluate their performance during a difficult asthma evaluation. Methods: MEDLINE was searched to identify key extra-pulmonary comorbidities that contribute to difficult asthma. Screening questionnaires were chosen based on ease of use, presence of a cut-off score, and adequate validation to help systematically identify comorbidities. In a consecutive series of 86 patients referred for systematic evaluation of difficult asthma, questionnaires were administered prior to clinical consultation. Results: Six difficult asthma comorbidities and corresponding screening questionnaires were found: sinonasal disease (allergic rhinitis and chronic rhinosinusitis), vocal cord dysfunction, dysfunctional breathing, obstructive sleep apnea, anxiety and depression, and gastro-oesophageal reflux disease. When the questionnaires were added to the referring clinicians impression, the detection of all six comorbidities was significantly enhanced. The average time for questionnaire administration was approximately 40 minutes. Conclusions: The use of validated screening questionnaires heightens detection of comorbidities in difficult asthma. The availability of data from a battery of questionnaires prior to consultation can save time and allow clinicians to systematically assess difficult asthma patients and to focus on areas of particular concern. Such an approach would ensure that all contributing comorbidities have been addressed before significant treatment escalation is considered.

Nonadherence in the era of severe asthma biologics and thermoplasty

Nonadherence to inhaled preventers impairs asthma control. Electronic monitoring devices (EMDs) can objectively measure adherence. Their use has not been reported in difficult asthma patients potentially suitable for novel therapies, i.e. biologics and bronchial thermoplasty. Consecutive patients with difficult asthma were assessed for eligibility for novel therapies. Medication adherence, defined as taking >75% of prescribed doses, was assessed by EMD and compared with standardised clinician assessment over an 8-week period. Among 69 difficult asthma patients, adherence could not be analysed in 13, due to device incompatibility or malfunction. Nonadherence was confirmed in 20 out of 45 (44.4%) patients. Clinical assessment of nonadherence was insensitive (physician 15%, nurse 28%). Serum eosinophils were higher in nonadherent patients. Including 11 patients with possible nonadherence (device refused or not returned) increased the nonadherence rate to 31 out of 56 (55%) patients. Severe asthma criteria were fulfilled by 59 out of 69 patients. 47 were eligible for novel therapies, with confirmed nonadherence in 16 out of 32 (50%) patients with EMD data; including seven patients with possible nonadherence increased the nonadherence rate to 23 out of 39 (59%). At least half the patients eligible for novel therapies were nonadherent to preventers. Nonadherence was often undetectable by clinical assessments. Preventer adherence must be confirmed objectively before employing novel severe asthma therapies. Preventer adherence is underrecognised and must be confirmed objectively prior to initiating novel asthma treatment http://ow.ly/Kc1X30iysYD

Burkholderia pseudomallei in cystic fibrosis and treatment complications.

A healthy 29‐year‐old Australian man with cystic fibrosis (CF) grew Burkholderia pseudomallei on a routine sputum culture 1 month after returning from holiday in Thailand. He underwent a 12‐month treatment regime with multiple antibiotics resulting in a number of adverse events. Sputum cultures were cleared of the pathogen and remain negative 8 years post‐treatment. There were no clinical sequelae and no deterioration in lung function. Few reports have been published to date on melioidosis in CF patients. The proposed management for this infection includes multiple antibiotics regimens for prolonged periods of time, which may result in adverse events. Optimal treatment and length of treatment are currently determined on an individual basis.

Treatable traits can be identified in a severe asthma registry and predict future exacerbations: Treatable traits in severe asthma

A new taxonomic and management approach, termed treatable traits, has been proposed for airway diseases including severe asthma. This study examined whether treatable traits could be identified using registry data and whether particular treatable traits were associated with future exacerbation risk.

Addressing ethnic disparity in asthma trials

Ethnic minorities experience poorer asthma outcomes. In Australia for example, there is a higher prevalence of asthma among Indigenous Australians when compared with other Australians. These Indigenous Australians with asthma have twice the rate of asthma hospitalizations. Indeed, asthma is the second most common reason for hospital admission among Indigenous Australians. Disturbingly, they also have three times the relative risk of asthma death. These ethnic disparities are not unique to Australia. Asthmatic individuals from other ethnic minorities such as African Americans and Maori in New Zealand face similar heightened risks. Such disparities are driven by a complex range of factors. This is best documented in the African American population, where first, African genetic ancestry amplifies the likelihood of developing asthma and influences the expression of disease phenotype. Second, physiology is different; African American patients perceive breathlessness less well, potentially masking the onset of asthma exacerbations. Third, lower socioeconomic status hinders health-care access. Fourth, social–environmental interactions impede medication adherence and compound obesity and smoking rates. Lastly, physician attitudes toward African American patients are worryingly negative, leading to qualitatively different medical consultations. Other ethnic minorities have not been as well studied as African Americans; however, existing data suggest many of these issues also apply to them. The factors discussed above combine to undermine effective asthma treatment. Recommended asthma action plans demand that a patient undertake a precise series of steps; early symptom recognition, adherence to agreed escalation and timely healthcare access. Yet these are the very issues where disadvantaged minorities struggle most. Medication efficacy may also vary across ethnic groups. Again, in African American asthma patients, in vitro responses to corticosteroids were diminished in T cells, findings that often reflect clinical steroid insensitivity. In a different study however, clinical responses of African Americans to inhaled corticosteroids (ICS) were preserved. More disquieting is evidence that African Americans fail treatment more frequently with long-acting beta-agonists, irrespective of concurrent ICS use. Underlying mechanisms for this remain unclear. Although betaadrenergic receptor polymorphisms do not seem to be responsible, other genetic variations may play a role. There is thus a tremendous potential for heterogeneity of asthma treatment effects in ethnic minorities. This makes their recruitment into mainstream trials a high priority, where they have traditionally been under-represented. A recent systematic review highlighted common barriers to study recruitment across four ethnic minorities. It also identified valuable facilitators to boost recruitment such as cultural congruence, community altruism and participant convenience. Even when substantial numbers of an ethnic minority are successfully recruited into asthma trials, a final challenge remains. Such trials are invariably powered to only detect a signal within the total cohort. Thus, subgroup analysis of ethnic groupspecific data is fraught with risks of type I (falsepositive) and type II (false-negative) error. Limiting the number of predefined analyses can reduce type I error. Ways of limiting type II error in this context will be discussed at the end of this article. In this issue of Respirology, Pilcher et al. report an important ethnic subgroup analysis of a large multicentre asthma trial. The parent study was a pragmatic randomized controlled trial, comparing combination budesonide/formoterol as maintenance and reliever therapy versus fixed-dose combination budesonide/formoterol plus as needed salbutamol, in individuals with poorly controlled asthma. One of the study’s strengths was the dispensing of metred dose inhalers with electronic monitoring, allowing accurate assessment of participants’ medication use. The study’s primary outcome was negative in that the frequency of at least one high-use episode of betaagonists was no different in the two arms. Secondary outcomes however were positive, with fewer days of high use of beta-agonists, and fewer severe asthma exacerbations in the budesonide/formoterol combination maintenance and reliever arm. Within this larger dataset, Pilcher et al. focus on the response of Maori patients. Three points are worthy of note. First, the authors should be congratulated for ethnic recruitment proportional to the New Zealand population. They enrolled 44 Maori out of the total 303 participants through culturally appropriate strategies. Second, their baseline data make sobering reading. Maori participants had worse symptom control, more prior hospitalizations, lower lung Conflict of interest: M.H. has received an unrestricted educational grant from Novartis, and sponsorship from Astra Zeneca in conducting an ultrasound course. bs_bs_banner

Working while unwell: Workplace impairment in people with severe asthma.

Severe asthma affects quality of life; however, its impact on workplace productivity is poorly understood.

Asthma or asthma-COPD overlap syndrome? - Reply: Correspondence

We read with great interest the article by Tay et al. about the relationship between co-morbidities and difficult asthma. The authors examined co-morbidities in 90 consecutive difficult asthma patients and found that co-morbidities independently impact a broad spectrum of outcomes such as frequent exacerbations, poor control and diminished quality of life in difficult asthma. This study increases our understanding of impact of all principal co-morbidities in a difficult asthma cohort. However, the patients involved in this study might need further discussion. First, we wonder whether the authors could provide the post-bronchodilator forced expiratory volume in 1 s (FEV1)% predicted or post-bronchodilator FEV1/forced vital capacity (FVC) ratio, which is important to identify whether the patients are ‘purely’ asthmatic or suffer from asthma-COPD overlap syndrome (ACOS). ACOS is characterized by persistent airflow limitation (FEV1 ≤ 80% predicted; FEV1/FVC ratio ≤70%) with several features shared with both asthma and COPD, including current or past smoking. If a portion of participants eligible for this difficult asthma study meet the criteria for ACOS patients, then subgroup analysis is required. For example, Ilmarinen et al. recently investigated the effect of systemic inflammation and co-morbidities on treatment and outcome of adultonset asthma, and they classified patients with suspected or coexisting COPD (post-bronchodilator FEV1/ FVC <0.7 and >10 smoked pack-years) as a separate ACOS group for comparison. Second, the definition of difficult asthma was made on the basis of diagnostic dilemma and poor symptoms. However, Robinson et al. published a systematic evaluation protocol of difficult-to-treat asthma, which showed that a significant proportion of patients have unidentified or alternative diagnoses. For a significant proportion of those patients identified and managed as such, treatment would have been straightforward. If this important differentiation was not made prior to this study, then a considerable number of patients entered in this study may not have had poor symptoms due to asthma.

Asthma or asthma-COPD overlap syndrome? – Reply

We read with great interest the article by Tay et al. about the relationship between co-morbidities and difficult asthma. The authors examined co-morbidities in 90 consecutive difficult asthma patients and found that co-morbidities independently impact a broad spectrum of outcomes such as frequent exacerbations, poor control and diminished quality of life in difficult asthma. This study increases our understanding of impact of all principal co-morbidities in a difficult asthma cohort. However, the patients involved in this study might need further discussion. First, we wonder whether the authors could provide the post-bronchodilator forced expiratory volume in 1 s (FEV1)% predicted or post-bronchodilator FEV1/forced vital capacity (FVC) ratio, which is important to identify whether the patients are ‘purely’ asthmatic or suffer from asthma-COPD overlap syndrome (ACOS). ACOS is characterized by persistent airflow limitation (FEV1 ≤ 80% predicted; FEV1/FVC ratio ≤70%) with several features shared with both asthma and COPD, including current or past smoking. If a portion of participants eligible for this difficult asthma study meet the criteria for ACOS patients, then subgroup analysis is required. For example, Ilmarinen et al. recently investigated the effect of systemic inflammation and co-morbidities on treatment and outcome of adultonset asthma, and they classified patients with suspected or coexisting COPD (post-bronchodilator FEV1/ FVC <0.7 and >10 smoked pack-years) as a separate ACOS group for comparison. Second, the definition of difficult asthma was made on the basis of diagnostic dilemma and poor symptoms. However, Robinson et al. published a systematic evaluation protocol of difficult-to-treat asthma, which showed that a significant proportion of patients have unidentified or alternative diagnoses. For a significant proportion of those patients identified and managed as such, treatment would have been straightforward. If this important differentiation was not made prior to this study, then a considerable number of patients entered in this study may not have had poor symptoms due to asthma.