Which people with severe asthma attend pulmonary rehabilitation? Insights from the German Asthma Net

Extract

Many people with severe asthma do not achieve complete asthma control and suffer from persistent symptoms such as dyspnoea and/or fatigue, difficulty performing work and daily activities, and/or frequent exacerbations. As a result, people with asthma often experience impaired quality of life, reduced lung function and exercise intolerance. Asthma is also a condition with a significant economic burden on society, which increases with poor disease control and greater disease severity [1].

Shareable abstract

Although its benefits have been clearly demonstrated, only 20.4% of individuals with severe asthma attended pulmonary rehabilitation (PR). PR attendees are characterised by reduced work ability and exercise capacity, and more symptoms and exacerbations. https://bit.ly/4fjzoo1

To the Editor:

Many people with severe asthma do not achieve complete asthma control and suffer from persistent symptoms such as dyspnoea and/or fatigue, difficulty performing work and daily activities, and/or frequent exacerbations. As a result, people with asthma often experience impaired quality of life, reduced lung function and exercise intolerance. Asthma is also a condition with a significant economic burden on society, which increases with poor disease control and greater disease severity [1].

In addition to comprehensive pharmacological treatment, pulmonary rehabilitation (PR) is a useful and important adjunct in the management of asthma. PR has been shown to improve exercise capacity, quality of life and asthma control [2–4] for individuals with asthma when it includes aerobic training, education or self-management. Furthermore, PR can reduce wheezing, anxiety, depression and bronchial inflammation [5]. Positive rehabilitation effects on physical performance and symptoms (dyspnoea and muscle fatigue) have also been demonstrated for people with severe asthma [6]. PR is therefore recommended for people with asthma to achieve long-term disease control and to reduce absence from work [7]. In addition to the individual benefits of PR, its services have been shown to be cost-effective in reducing symptoms and hospital admissions, thereby addressing the economic burden of the disease [8].

Despite its benefits, only a small proportion of people with asthma are thought to be offered PR [9]. As precise attendance rates in people with asthma are unknown, the aim of this analysis was to evaluate, in a large, national cohort, how many people with severe asthma attend PR and to characterise these patients.

For this analysis, clinical data from the German Asthma Net (GAN) register for severe asthma were used (Ethics Committee of Rhineland-Palatinate Medical Association: 837.366.11 [7908]; www.clinicaltrials.gov identifier number NCT06035289) which were collected prospectively, after informed consent, at registry entry and during annual follow-up visits. Inclusion criteria were adults with severe asthma, which was defined by a high or medium level of treatment and poor symptom control (Global Initiative for Asthma (GINA) step 5 [10]), enrolled in GAN centres in Germany between 2011 and 2023, and data on participation in PR at any time point. Patients who had completed PR in the last 12 months prior to any visit were defined as the “PR group” (PRG), whereas patients who had never attended PR were defined as the “control group” (CON). Data from the most recent visit (CON) or the visit before PR (PRG) were used for this retrospective cross-sectional analysis.

The data were checked for consistency and normality. Categorical parameters were analysed using the Chi-squared test and continuous parameters using the Mann–Whitney U-test. Potential predictors of PR attendance for multiple logistic regression analysis were selected based on clinical judgement and data availability: age, GINA control status, Asthma Control Test, work disability, exacerbation rate, comorbidities and symptoms (table 1). All statistical analyses were two-sided with a significance level (α) of 0.05. All analyses were performed using SAS 9.4 statistical software (TS1M6) (Cary, NC, USA) for Microsoft Windows (Redmond, WA, USA).

TABLE 1.

Differences in characteristics between the pulmonary rehabilitation group (PRG) and the control group (CON)

	PRG	CON	Between-group difference, mean (95% CI)	p-value
Patients, n	528	2058
Age, years	52.7±13	55.7±14.5	3.07 (1.71–4.43)	0.0001
Male gender	195 (38.2)	826 (41.6)		0.1620
FEV1, % pred	64.1±22.8	69.1±21.8	4.97 (2.80–7.15)	0.0001
FVC, % pred	77.6±20.7	81.4±29.9	3.81 (0.98–6.64)	0.0084
DLCO, %	70.0±16.7	73.2±16.8	3.15 (0.67–5.62)	0.0127
FENO, ppb	43.3±45.9	45.2±48.5	1.85 (−4.34–8.04)	0.5584
ACQ score#, points	2.9±1.5	2.3±1.5	0.62 (0.46–0.79)	0.0001
ACT score, points	14.3±5.6	16.5±5.8	2.21 (1.64–2.79)	0.0001
Allergic comorbidities	292 (64.2)	762 (59.7)		0.2389
Asthma phenotype				0.2891
Predominantly allergic asthma	126 (42.0)	314 (37.3)
Nonallergic asthma	90 (30.0)	258 (30.6)
Mixed forms of asthma	84 (28.0)	270 (32.1)
α1-Antitrypsin deficiency	1 (0.4)	9 (0.4)		0.4137
Vocal cord dysfunction	8 (1.5)	7 (0.3)		0.0015
GINA control status				0.0001
Controlled	82 (15.5)	491 (23.9)
Partly controlled	128 (24.2)	632 (30.7)
Uncontrolled	318 (60.2)	934 (45.4)
miniAQLQ score, points	3.76±1.29	4.42±1.48		0.0001
Workability	194 (36.7)	1192 (57.9)		0.0001
Symptoms
Exertional dyspnoea	438 (83.0)	1463 (71.1)		0.0001
Resting dyspnoea	119 (22.5)	311 (15.1)		0.0001
Chest tightness	146 (27.7)	446 (21.7)		0.0035
Coughing	285 (54.0)	985 (47.9)		0.0122
Rhonchus/wheezing	214 (40.5)	614 (29.8)		0.0001
Prolonged expiration	73.0 (13.8)	173 (8.4)		0.0002
Reduced exercise capacity	381 (72.2)	1175 (57.1)		0.0001
Bronchial hyperresponsiveness	362 (68.6)	1140 (55.4)		0.0001
Depression	126 (23.9)	291 (14.1)		0.0001
Frequency of exacerbations, cases (%)
None	124 (23.9)	996 (47.4)		0.0001
1 per year	86 (16.6)	266 (13.0)
2–11 per year	249 (48.0)	630 (30.8)
≥1 per month	45 (8.7)	81(4.0)
Unknown	15 (2.9)	99 (4.8)
Use of medical services in last 12 months, cases (%)
Emergency care	223 (58.1)	439 (44.0)		0.0001
Hospitalisation	180 (46.9)	220 (22.1)		0.0001
Hospitalisation with intensive care	47 (12.3)	54 (5.4)		0.0001

Data are presented as mean±sd or n (%) unless otherwise stated. Symptoms were surveyed and sought by the physician. Between-group differences were calculated for all numerical data. FEV₁: forced expiratory capacity in 1 s; FVC: forced vital capacity; D_LCO: diffusion capacity of the lung for carbon monoxide; F_ENO: exhaled nitric oxide fraction; ACQ: Asthma Control Questionnaire; ACT: Asthma Control Test; GINA: Global Initiative for Asthma; miniAQLQ: mini Asthma Quality of Life Questionnaire. ^#: 0–6 points. Significant results are marked in bold.

2586 individuals with severe asthma were included in this analysis (mean±sd 55±14 years, 41% male and mean forced expiratory volume in 1 s 68.0±22.1% pred). During the observation period, 20.4% of patients (n=528) attended PR at least once. As inpatient PR with a duration of 3 weeks is the most common setting in Germany, it was used in 85.3% of cases. 5.2% of patients used an outpatient setting (9.4% unknown). 19.7% of patients (n=509) attended in one and 0.7% patients (n=19) in more than one PR programme in the previous 12 months.

A comparison between PRG and CON showed that PRG patients were younger, and had more impaired lung function and poorer asthma control (table 1). The pharmacological therapy included biologics, antibody therapies (mepolizumab, benralizumab, reslizumab, dupilumab, omalizumab and tezepelumab) at a similar rate in PRG and CON (52.3% and 54.8%, p=0.2964). The response to treatment with biologics was significantly different between both groups: 64.5% (CON) versus 51.8% (PRG) (p=0.0001) have been recognised as responders, as defined by the clinical evaluation of the treating physician, independently of the product used.

Multiple logistic regression analysis showed that a reduced ability to work (OR 2.405, p<0.0001), a reduced exercise capacity (OR 1.288, p=0.0412), exacerbations in the last 12 months (OR 2.171, p<0.0001), symptoms of depression (OR 1.728, p≤0.0001) and exertional dyspnoea (OR 1.313, p=0.0627) had a significant influence on attending PR. Simple logistic regression analysis showed that if an exacerbation had occurred in the previous 12 months, the odds of attending a PR were 28% compared to 11% without an exacerbation.

Data from this large, nationwide cohort showed that only a minority (20.4%) of individuals with severe asthma attended PR, although its benefits are well proven for several outcomes and different stages of disease and they were likely to benefit [4]. We found significant differences between patients attending PR and those patients who never attended PR. PRG individuals had, for example, poorer lung function or asthma control and a reduced response to biologic therapy compared to CON. The inability to work, reduced exercise capacity, exacerbations in the past and higher symptom burden (depression and dyspnoea) were factors that predicted PR participation. In fact, some of these characteristics (low exercise capacity and high perception of dyspnoea) have been described to correlate to PR success in asthma [11]. Therefore, in this cohort, it seems that the right persons with the highest probability to benefit received the right interventions. Additionally, all these factors certainly increase the patients’ suffering and apparently favour PR participation.

Exacerbations demonstrated the strongest impact on PR participation. The occurrence of an exacerbation in the last year increases the likelihood of participating in PR to 28%, while not experiencing an exacerbation makes PR participation much less likely (11%). Since all GAN centres recommend PR when including people with asthma in the registry regardless of the occurrence of an exacerbation, we assume that exacerbated patients are more willing to follow medical PR recommendations than nonexacerbated patients. Through PR, individuals with asthma can achieve lower exacerbation rates and better symptom control; for example, by learning how to avoid typical triggers, recognising an exacerbation early and managing it appropriately on an individual basis. Given the impact of exacerbations on asthma morbidity and healthcare costs, approaches to prevent these events, even in nonexacerbators, are necessary and cost-efficient [12].

To our knowledge, there are no data available on the PR attendance rate in individuals with severe asthma. However, the poor PR uptake rate is also known from other chronic lung diseases such as COPD [13]. The COSYCONET registry detected that only 34% of people with COPD had ever attended PR [14]. Data from countries with predominantly outpatient PR settings give a very wide range of 0–85% attendance rate in individuals with COPD [15]. In general, the lack of PR awareness among healthcare professionals is discussed as the primary reason for nonreferral to PR [16]. At the GAN centres, PR recommendation to people with severe asthma is part of the clinical routine (both oral and written). In this case, major barriers appear to be the time-consuming administrative effort involved in applying for PR and regular rejection by health insurance providers. Individual barriers can also influence whether patients participate in PR. In particular, patients who cannot leave their home environment for an inpatient programme (e.g. due to relatives to be cared for) and who cannot make use of disease-specific PR in the vicinity (only 5.2% used outpatient programmes in this cohort) are often denied PR. Theoretically, this problem could be reduced through telehealth programmes [17], which could enable each patient to choose the setting that suits best the individual needs (patient choice), and might increase PR participation and completion rate. However, in clinical practice, infrastructure for a spectrum of models of PR must still be significantly expanded and offered with the corresponding quality standards to be safe and effective.

It should be noted that our analysis only includes cases where PR was completed. There are no data available on early PR termination, or PR offers or refusals. Additionally, depending on the healthcare system and clinical routines, these results from predominantly inpatient PR may not be generalisable.

In order to make PR available to a wider target group, it is necessary to identify and reduce the barriers that lead to nonparticipation in PR. Increasing awareness of the benefits of PR among patients, healthcare providers and healthcare professionals would help to get patients into PR earlier and allow them to be trained in how to prevent or mitigate exacerbations. It should be ensured that patients who need PR have access to it.