T. van der Molen

Quality of life during formoterol treatment : Comparison between asthma-specific and generic questionnaires

This study aimed to investigate the effect of treating patients with moderate asthma with formoterol on quality of life (QoL) and to compare several questionnaires in their ability to detect changes in QoL. In an eight month multicentre, randomized, placebo-controlled trial, patients with asthma using daily inhaled corticosteroids and beta2-agonists (> or = 5 inhalations x week(-1)) were randomized to 6 months treatment with formoterol 24 microg b.i.d. (by Turbuhaler) or a matching placebo. Patients recorded symptoms (maximal score 21) and peak expiratory flow (PEF) twice daily. QoL was measured with two asthma-specific questionnaires, the Asthma Quality of Life Questionnaire (AQLQ) and the Living with Asthma Questionnaire (LWAQ), and with two generic QoL forms, i.e. the Short Form 36 (SF36) and the Psychological and General Well-Being scale (PGWB) at randomization and after 6 months of treatment. Out of 110 patients studied, 56 received formoterol and 54 placebo. Mean baseline forced expiratory volume in one second was 65% predicted. Mean morning PEF was 369 L x min(-1). Mean total symptom score was 3.6. Morning PEF increased (26.8 L x min(-1), p=0.0001) and symptoms decreased (-1.23, p=0.012) in the formoterol group in contrast to placebo. QoL improvements were measured in the LWAQ total score (baseline 0.61, change -0.05, p=0.048) and the physical construct of the LWAQ (baseline 0.71, change 0.07, p=0.044). The AQLQ and the generic QoL instruments showed no significant changes. In conclusion, the improvement in quality of life reported after 6 months was very small and only reflected by the Living with Asthma Questionnaire.

Physical activity is increased by a 12-week semiautomated telecoaching programme in patients with COPD: a multicentre randomised controlled trial

Rationale Reduced physical activity (PA) in patients with COPD is associated with a poor prognosis. Increasing PA is a key therapeutic target, but thus far few strategies have been found effective in this patient group. Objectives To investigate the effectiveness of a 12-week semiautomated telecoaching intervention on PA in patients with COPD in a multicentre European randomised controlled trial. Methods 343 patients from six centres, encompassing a wide spectrum of disease severity, were randomly allocated to either a usual care group (UCG) or a telecoaching intervention group (IG) between June and December 2014. This 12-week intervention included an exercise booklet and a step counter providing feedback both directly and via a dedicated smartphone application. The latter provided an individualised daily activity goal (steps) revised weekly and text messages as well as allowing occasional telephone contacts with investigators. PA was measured using accelerometry during 1 week preceding randomisation and during week 12. Secondary outcomes included exercise capacity and health status. Analyses were based on modified intention to treat. Main results Both groups were comparable at baseline in terms of factors influencing PA. At 12 weeks, the intervention yielded a between-group difference of mean, 95% CI (lower limit – upper limit; ll-ul) +1469, 95% CI (971 to 1965) steps/day and +10.4, 95% CI (6.1 to 14.7) min/day moderate PA; favouring the IG (all p≤0.001). The change in 6-min walk distance was significantly different (13.4, 95% CI (3.40 to 23.5) m, p<0.01), favouring the IG. In IG patients, an improvement could be observed in the functional state domain of the clinical COPD questionnaire (p=0.03) compared with UCG. Other health status outcomes did not differ. Conclusions The amount and intensity of PA can be significantly increased in patients with COPD using a 12-week semiautomated telecoaching intervention including a step counter and an application installed on a smartphone. Trial registration number: NCT02158065.

Effects of small airway dysfunction on the clinical expression of asthma: a focus on asthma symptoms and bronchial hyper-responsiveness.

The small airways are an important site of inflammation in asthma. However, the relation between small airway dysfunction and clinical expression of asthma has hardly been studied.

Less small airway dysfunction in asymptomatic bronchial hyperresponsiveness than in asthma

Bronchial hyperresponsiveness (BHR) can be present in subjects without any respiratory symptoms. Little is known about the role of the small airways in asymptomatic subjects with BHR.

Combining genomewide association study and lung eQTL analysis provides evidence for novel genes associated with asthma

Genomewide association studies (GWASs) of asthma have identified single‐nucleotide polymorphisms (SNPs) that modestly increase the risk for asthma. This could be due to phenotypic heterogeneity of asthma. Bronchial hyperresponsiveness (BHR) is a phenotypic hallmark of asthma. We aim to identify susceptibility genes for asthma combined with BHR and analyse the presence of cis‐eQTLs among replicated SNPs. Secondly, we compare the genetic association of SNPs previously associated with (doctors diagnosed) asthma to our GWAS of asthma with BHR.

COPD: early diagnosis and treatment to slow disease progression.

SummaryAims Chronic obstructive pulmonary disease (COPD) is usually a progressive condition. Undiagnosed early-stage disease, particularly in symptomatic patients, is likely to become more severe with time. Hence, prevention or reduction in disease progression is highly relevant. We evaluated the published data and discussed the potential impact of early intervention on the course of COPD. Methods We performed PubMed searches of studies in early or mild COPD, focusing on those relating to lung function decline. Results Smoking cessation reduced lung function decline at all stages of COPD, and the earlier the intervention, the greater the impact on lung function. Accumulating data from placebo-controlled trials suggested that long-acting bronchodilators can slow the decline in lung function, as well as reduce exacerbation and mortality rates and improve health-related quality of life (HRQoL) in patients with mild-to-moderate COPD. Inhaled corticosteroids (ICS) do not impact lung function in early COPD, and further research is needed on the role of long-acting β2-agonist-ICS combination therapy in these patients. Conclusions Initiating treatment early in the course of COPD is likely to slow disease progression and improve HRQoL. Current data support maintenance treatment with a long-acting bronchodilator in this patient group. However, many questions remain unanswered regarding the optimal treatment of mild COPD, and further research is required to develop evidence-based recommendations in this field.

Feasibility and applicability of the paper and electronic COPD assessment test (CAT) and the clinical COPD questionnaire (CCQ) in primary care: a clinimetric study

Three questionnaires are recommended in the management of chronic obstructive pulmonary disease by the global initiative for obstructive lung disease, of which two are the more comprehensive assessments: the chronic obstructive pulmonary disease assessment test and the clinical chronic obstructive pulmonary disease questionnaire. Both are carefully designed high-quality questionnaires, but information on the feasibility for routine use is scarce. The aim of this study was to compare the time to complete the chronic obstructive pulmonary disease assessment test and the clinical chronic obstructive pulmonary disease questionnaire and the acceptability of the questionnaires. Furthermore, the agreement between electronic and paper versions of the questionnaires was explored. The time to complete the electronic versions of the questionnaires was 99.6 [IQR 74; 157] vs. 97.5 [IQR 68; 136] seconds for clinical clinical chronic obstructive pulmonary disease questionnaire and chronic obstructive pulmonary disease assessment test, respectively. The difference in time to complete the questionnaire was not significant. The two questionnaires did not differ in “easiness to complete” or “importance of issues raised in questionnaires”. Electronic vs. paper versions revealed high agreement (ICC CCQ = 0.815 [0.712; 0.883] and ICC CAT = 0.751 [0.608; 0.847]) between the administration methods. Based on this study it can be concluded that both questionnaires are equally suitable for use in routine clinical practice, because they are both quick to complete and have a good acceptability by the patient. Agreement between electronic and paper versions of the questionnaires was high, so use of electronic versions is justified.COPD: questionnaires equally suitable for clinical practiceTwo questionnaires commonly used to manage chronic obstructive pulmonary diseases (COPD) are equally suitable for routine primary care. Researchers in The Netherlands, led by Janwillem Kocks from the University Medical Center Groningen, administered both the COPD assessment test (CAT) and the clinical COPD questionnaire (CCQ) to 95 patients with the lung disease. These two tests are the most comprehensive assessments recommended by the global initiative for obstructive lung disease for guiding treatment decisions. The researchers found that both tests took approximately 95–100 s on average. Both tests were also equally easy to complete and provided similar types of information. Most patients said they had no preference for either one, and they filled out both electronic and paper versions of the questionnaires in much the same way. The authors conclude that both tests seem fine for routine use.

Use of the Control of Allergic Rhinitis and Asthma Test (CARATkids) in children and adolescents; validation in Dutch

Allergic rhinitis and asthma are common and closely related diseases. Recently, a Portuguese questionnaire has been developed ‘The Control of Allergic Rhinitis and Asthma Test’ (CARATkids) that measures disease control of both diseases in children. This study aims to validate the CARATkids in Dutch children and for the first time in adolescents and, in addition, to calculate the minimal clinically important difference (MCID).

Small airway dysfunction in asymptomatic bronchial hyperresponsiveness and asthma

We read with great interest the article by Boudewijn et al. (1), who compared the small airway dysfunction in healthy controls, subjects with asymptomatic airway hyperresponsiveness, and patients with asthma. We are grateful to the authors for their insights into advancing our understandings of the changes in small airway indices prior to and following methacholine bronchial inhalation challenge as well as their relationship with sensation of dyspnea. We respectfully disagree with the way in which the data were presented. First, the small airway dysfunction seemed to be defined as the presence of either of the aberrant small airway indices in the present study. Although the ‘gold criteria’ for defining small airway dysfunction are lacking, a combination of miscellaneous techniques (i.e., interrupter technique, helium–oxygen mixed gas ventilation, biopsy) may be preferred (2), or alternatively, this should be stated as a major limitation of the study. Second, we found that the changes in small airways caliber following methacholine inhalation challenge were better reflected by resonant frequency (Fres) and the area of reactance integrated from 5Hz to Fres (AX), but not R5–R20, in patients with different levels of asthma control (W.-J. Guan and J.-P. Zheng, unpublished data). This suggested that the frequency dependence should be preferentially employed to determine the degree of small airway dysfunction, particularly in those with asymptomatic airway hyperresponsiveness. Third, the changes in forced vital capacity (FVC) should be explicitly stated, for it represented the degree of air trapping or ventilation heterogeneity as a consequence of small airway dysfunction. The readers might be perplexed by the issue as to whether FVC remained normal following inhalation challenge, and if so, the conclusion that a greater change in small airway indices indicated a more pronounced small airway dysfunction could then be safely made. A surrogate approach could be the measurement of residual volume (RV) and the ratio of RV to total lung capacity (TLC) following inhalation challenge, as the authors did at the baseline measurement only. Furthermore, patients with asthma had a mean FEV1 of 101% predicted, suggesting that they had a very limited magnitude of small airway dysfunction. The bronchial inhalation challenge test might have been precluded because those with moderate to severe asthma, who had more pronounced small airway dysfunction, did not meet the eligibility for enrollment. Apart from the aforementioned pitfalls, some other remarks are made. Airway hyperresponsiveness could be, to our knowledge, significantly influenced by the stimuli insults, for instance cigarette smoking. In this cohort, 53% of subjects with asymptomatic airway hyperresponsiveness were current smokers, and this figure was significantly higher than that in patients with asthma (13%) and healthy controls (33%). This was likely to generate a bias toward the small airway dysfunction detected by impulse oscillometry. Moreover, although it would be reasonable to link the changes in small airway indices to the Borg’s score of dyspnea at PC20, the correlation analysis has been, as determined by its inherited demerits, difficult to fully elucidate the causative effects. And the hypothesis that the dyspnea sensation was influenced by small airways was, at least partly, dampened by the observations in patients with asthma who did not yield statistically significant correlations, although several potential confounders have been mentioned in the authors’ discussion. Once these issues have been appropriately addressed, we could explore deeper into the roles that small airways play in the development of asymptomatic airway hyperresponsiveness and the sensation of dyspnea. This is expected to call for further research on the early intervention of mildest form of asthma. A study that compares the utility of different small airway indices on identifying subjects with asymptomatic airway hyperresponsiveness and reflecting the level of asthma control is also necessary.

P116 Observational study to characterise 24-hour COPD symptoms: cross-sectional results from the ASSESS study

Introduction and Objectives Little is known about the 24-hour profile of COPD symptoms. This study assessed the frequency/severity of 24-hour symptoms and their impact on patients’ well-being. Methods This cross-sectional, observational study was conducted in patients with stable COPD. Baseline night-time, early-morning and day-time symptoms (symptom questionnaire), dyspnoea (modified Medical Research Council dyspnoea scale [mMRC]), health status (COPD Assessment Test [CAT]), anxiety/depression levels (Hospital Anxiety and Depression Scale [HADS]) and sleep quality (COPD and Asthma Sleep Impact Scale [CASIS]) were assessed. Primary endpoint: baseline frequency, severity and inter-relationship of night-time, early-morning and day-time symptoms; secondary endpoints: relationship between 24-hour symptoms and dyspnoea, health status, anxiety/depression and sleep quality. Results 727 patients were recruited from eight countries: 65.8% male, mean ± SD age 67.2 ± 8.8 years, mean ± SD% predicted FEV1 52.7 ± 20.6%. Early-morning/day-time symptoms were most frequent; however night-time symptoms were common (Table). Symptom severity was comparable during the night-time, early-morning and day-time. In the week prior to baseline, 56.7% patients had symptoms throughout the 24-hours (79.9% in 2 or 3 parts of the day). Breathlessness was most common (71.4% patients); its prevalence increased throughout the 24-hours (32.1% night-time, 51.6% early-morning, 65.2% day-time). Dyspnoea, health status, anxiety/depression and sleep quality were worse in patients with night-time, early-morning or day-time symptoms versus patients without symptoms in each period (all p < 0.001). Most patients with more severe dyspnoea (mMRC scale ≥2) had 24-hour symptoms (range 61.5–68.2%); patients with 24-hour symptoms had the worst health status (mean CAT score 20.0 vs range 8.1–14.9 in all other patients). Patients with any combination of night-time/early-morning symptoms had the highest anxiety (mean HADS scores 6.7–7.5 vs 3.6–5.8 in patients without this combination); depression levels were lowest in patients with no symptoms/only early-morning symptoms (mean HADS scores 4.2–5.4 vs 6.5–7.8 in all other patients). Patients with any night-time symptom had worse sleep quality than patients without night-time symptoms (mean CASIS scores 41.6–51.1 vs 31.6–35.5). Conclusions Most patients had COPD symptoms throughout the 24-hours. Dyspnoea, health status, anxiety/depression levels and sleep quality were significantly worse in patients who had symptoms in any part of the day. Abstract P116 Table 1. Prevalence and severity of COPD symptoms throughout the 24-hour day N=727 Night-time Early-morning Day-time Prevalence of COPD symptoms, n (%) ≥3 times during the past week 312 (42.9) 455 (62.6) 427 (58.7) ≥3 times during a typical weeka 378 (52.0) 488 (67.1) 468 (64.4) ≥1 COPD symptoms during the past week 458 (63.0) 592 (81.4) 601 (82.7) Severity of COPD symptoms,b n (%c) Mild 191 (46.7) 252 (44.1) 254 (43.1) Moderate 175 (42.8) 250 (43.8) 272 (46.2) Severe 39 (9.5) 61 (10.7) 59 (10.0) Very severe 4 (1) 8 (1.4) 4 (0.7) a A typical week refers to a week that the patient considers is most usual for them during the previous month b During the previous week c Percentage based on patients who reported symptoms in the previous week and provided data for symptom severity