Abbreviations:

CPT- chest physiotherapy; CF- cystic fibrosis; NCFB- non-cystic fibrosis bronchiectasis; PEP- positive expiratory pressure; UK- United Kingdom; USA- United States of America; ABPA- allergic bronchopulmonary aspergillosis; GERD- gastro-esophageal reflux disease; CFRD- cystic fibrosis related diabetes mellitus; COPD- chronic obstructive pulmonary disease; HRQoL- Health-related quality of life; LCQ- Leicester Cough Questionnaire; SGRQ- St George's Respiratory Questionnaire; FEV¹- forced expiratory volume in 1 second; FVC- forced vital capacity; PRISMA- Preferred Reporting Items for Systematic Reviews and Meta-Analyses; MeSH- Medical Subject Headings; BMI- mean body mass index; QoL- quality of life; HFCWO- High frequency chest wall oscillation; BMQ- Beliefs about Medicine Questionnaire; ACT- Airway clearance technique; HFCWO- High-frequency chest wall oscillating device; FD- flutter device; PEP- Positive expiratory pressure devices; ACBT- active cycle breathing technique; AD- autogenic drainage; P+PD- Percussion and postural drainage; MARS- Medication Adherence Report Scale; HBM- Health Belief Model; QoL-B- Quality of Life Questionnaire-Bronchiectasis; DPD- Daily Phone Diary

1. Introduction

Non-cystic fibrosis bronchiectasis (NCFB) is a chronic respiratory disease with abnormal permanent dilatation of bronchi [1]. It is characterised by a variety of symptoms, including, cough, excess sputum production, dyspnoea, weight loss, haemoptysis, airway inflammation and recurrent chest infections [2]. The disease can be caused by many aetiologies which are often unidentifiable and idiopathic [3, 4]. In adults, previous pulmonary infections constitute a significant proportion of the aetiologies of NCFB [3, 5]. The other less common aetiologies include immune-related causes, allergic bronchopulmonary aspergillosis (ABPA), connective tissue disease, gastro-esophageal reflux disease (GERD) and sinobronchial syndrome [3]. The major cause of bronchiectasis in the younger population is cystic fibrosis (CF). CF is a genetic disease that results in chronic progressive obstructive lung disease and manifests itself systemically through nutrient malabsorption, liver cirrhosis and CF-related diabetes mellitus (CFRD). CF is not curable and therefore, the focus of the treatment is on the optimisation and maintenance of lung function, as well as the reduction of exacerbations and morbidities [6].

The prognosis of patients with NCFB is poor with mortality rates of 10.6% over a 3.5-year period, 20.4% over a 5-year period and 29.7% over a 13-year period [7-10]. The main cause of deaths was respiratory failure secondary to respiratory infections [9, 10]. Although the global prevalence of NCFB is largely unknown, the trend of prevalence of NCFB is increasing worldwide [3, 11, 12]. The management of it is challenging with limited treatment options. The treatment of NCFB focuses on airway clearance, treatment of chest infections and prevention of exacerbations such as influenza vaccination [13]. Chest physiotherapy (CPT) facilitates airway clearance of secretions and is widely promoted as the key component in the management of bronchiectasis [13]. Antibiotics are used to treat acute exacerbations, eradicate infections, reduce bacterial load and suppress infections [1, 14]. Bronchodilators are used for patients with concomitant respiratory conditions such as asthma and chronic obstructive pulmonary disease (COPD).

The British Thoracic Society (BTS) guidelines for NCFB in adults recommend twice daily CPT for patients with persistent productive cough [15]. There are many different types of CPT techniques, such as postural drainage, chest wall percussions, vibrations, as well as, using positive expiratory pressure devices (e.g. Acapella, Flutter) [16, 17]. The adherence rate to CPT ranges from 14% to 60%, and is influenced by the treatment modality [18, 19]. The outcomes of NCFB treatment on health-related quality of life (HRQoL) can be evaluated by the Leicester Cough Questionnaire (LCQ) and St George's Respiratory Questionnaire (SGRQ), with both including symptoms of exacerbation [20, 21]. Other methods of evaluating the effectiveness of treatment include measuring forced expiratory volume (FEV¹) in 1 second (i.e. FEV¹% predicted), forced vital capacity (FVC) and exercise tolerance.

In the study of CPT, although there is a lack of studies with good methodological quality in demonstrating its efficacy and effectiveness, regular CPT has been broadly advocated in international guidelines as a pillar of the management of bronchiectasis. Poor adherence to treatment is well recognized, and significantly contributes to treatment failures in medical interventions. Therefore, it is imperative to examine factors influencing adherence to CPT in patients with bronchiectasis. Additionally, as there are very few evidence based treatment for bronchiectasis, it is also important to determine if CPT plays a role on the disease progression, lung function, exacerbations and quality of life of patients with bronchiectasis [22]. We undertook a literature review to determine whether compliance with CPT influences the clinical outcomes of patients and if it is associated with the duration of CPT treatment.

2. Materials and Methods

A systematic literature review was conducted with the aim of identifying publications that reported the adherence rates to CPT in patients with either CF or NCFB. This was done in accordance with the Cochrane Handbook of Systematic Reviews and Meta-analysis and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines [23].

2.1 Search criteria

The present study was based on a search of the Pubmed, Embase and Cochrane databases using a combination of Medical Subject Headings (MeSH) and non-MeSH key terms with Boolean operator as shown in Table 1. The following search strategy was used: (“Bronchiectasis” OR “Cystic Fibrosis” OR “Cystic fibrosis bronchiectasis”) AND (“Chest Physiotherapy” OR “Chest Physical Therapy” OR “Airway Clearance” OR “Respiratory Therapy”) AND (“Compliance” Or “Adherence” OR “Persistence” OR “Daily treatment”). All searches underwent double-blind screening by three researchers (J.S.Tan, A.Y.H. Low, A.Y.H. Lim) and full-text articles of potentially appropriate abstracts were reviewed. Duplicates were removed and conflicts were resolved by consensus. Search strategy was supplemented by review of reference lists, bibliographies including the BTS guidelines and investigator files. A PRISMA flow diagram of the review and selection of articles is shown in Figure 1.

Table 1: Search strategy.

2.2 Study Inclusion and Exclusion Criteria

All studies were considered eligible if they fulfilled the following criteria: original publications, inclusion of a cohort of patients with CF or NCFB, adherence rates to CPT reported. Abstracts, letters to editors, case study reports, review papers and non-English language papers were excluded.

2.3 Data Extraction

Data was extracted from selected papers using a standardised method into a preformatted database by a single researcher. All extracted data was then verified by a second researcher. Any disagreement between investigators was resolved independently by a third investigator. Data extracted for study design and patient demographics included author name, year of publication, study design, treatment modalities, study population, mean age, gender and mean percent predicted FEV¹ (Table 2). Data extracted regarding adherence includes the methods used to measure adherence, adherence criteria, adherence rates and other findings/outcomes associated with adherence (Table 3).

3. Results

A total of 1794 articles were identified. Of these, 92 articles were screened in full paper review after excluding articles during title and abstract review. During the full paper review, 79 articles were excluded and 13 articles fulfilled the criteria for the systemic review (Figure 1) [19, 24-36]. The characteristics of the thirteen included studies are shown in Table 2. There were eight cross-sectional studies, three prospective studies, one interview-based study, one was a combination of a randomized clinical trial and a retrospective study (Table 2). All the studies were on CF patients apart from one study on NCFB patients. There were a total of 990 patients involved in the 13 studies with sample sizes ranged from 36 to 153 participants. Eight studies were conducted in the United States of America (USA) [26, 27, 31-36] two in Northern Ireland [24, 30], two in Brazil [19, 29], and one in Canada [28]. The mean age of paediatric and adult study populations ranged from 11.2 to 12.2 years and 28.2 to 64 years respectively (Table 2). The study duration ranged from 1 to 16 months. Five (38.5%) studies reported the type of chest physiotherapy modalities [24-27, 29, 30, 32, 33, 35]. High frequency chest wall oscillation (HFCWO) therapy was assessed in two studies [31, 36] and a variety of airway clearance devices were assessed in three studies [19, 28, 34]. The adherence rates were measured by either using a self-reported questionnaire, daily phone diary or a built-in chronometer.

In terms of study outcomes, five studies reported on the association between adherence and lung function [24, 29, 31, 34, 36]. One study reported hospitalization rates and duration of stay in hospital [29]. Two studies reported on the association between adherence and quality of life [24, 29]. Four studies reported on the barriers to adherence [19, 29, 32, 33]. Ten studies reported on patient’s perceptions and/or its association with adherence [26-30, 32-36]. Three studies compared adherence rates amongst various types of CPT [19, 28, 34].

Figure 1: PRISMA flow diagram of the review and selection of articles.

(#) Seventy seven articles were excluded as they do not report adherence rate on CPT, literature review papers, abstracts and non-English language papers; (*) Two articles were excluded as limited data on adherence to CPT provided and duplicated cohort

Table 2: Study design and demographics of study population.

3.1 The rate of adherence on CPT

The rate of adherence of CPT in the paediatric study population was higher than the adult study population (mean range: 51% to 61% vs. 41% to 51% respectively) [24, 28, 29, 30, 35, 36]. The CPT modalities associated with the highest rate of adherence was flutter device (83.3%), followed by positive expiratory pressure (PEP) (68.8%), active cycle of breathing (34%), autogenic drainage (28.6%), percussion and autogenic drainage (14.3%) [19]. Adolescents with CF were more likely to achieve moderate adherence with flutter devices compared with percussion and postural drainage and HFCWO therapy [28, 34]. The method of assessment of adherence varied widely across studies. Some studies stratified patients into high, moderate and low adherence groups [19, 34, 36]. Whilst other studies stratified patients into adherent or non-adherent groups [24, 28, 30, 32, 33, 35]. This causes comparison of adherence rates across studies to be more challenging.

3.2 The effect of adherence of CPT on lung function and pulmonary exacerbations

The effect of adherence to CPT on lung function varied amongst studies (Table 3). Three studies reported no significant association between adherence and lung function [24, 29, 36]. However, 2 other studies reported a positive association between percent predicted FEV¹ and the rate of adherence to CPT [31, 34]. It was found that patients with better lung function felt a lesser need to be compliant to CPT [19]. Feiten and co-workers reported that low adherence to CPT was associated with patients who had advanced lung disease and frequent hospitalizations [29]. Pulmonary exacerbation rate was assessed in two studies [24, 31]. One study reported fewer pulmonary exacerbations among patients with higher adherence to CPT [31]. Meanwhile, the other study reported no association between pulmonary exacerbations and adherence to CPT [24].

3.3 The effect of adherence of CPT on the quality of life

Two studies reported on the association between quality of life (QoL) and adherence to CPT [24, 29]. McCullough and co-workers reported that adherence to CPT was associated with a higher burden of treatment and a poorer QoL [24]. The same study reported that patients with more symptoms were more likely to adhere to CPT. Conversely, Feiten and co-workers reported that patients with moderate or poor adherence to CPT were associated with a lower score of QoL on the domains of emotion, physical, treatment burden, health perceptions, social and respiratory functioning [29].

3.4 Patients’ perceptions and socio-economic status

Ten studies reported on the association between patients’ perceptions of CPT, adherence to CPT, and or barriers to adherence [26-30, 32-36]. Factors affecting perception of CPT were the perceived importance of CPT, patients’ understanding of the treatment, difficulty of use and self-efficacy. Children whose parents had strong beliefs regarding their child’s use of CPT were significantly associated with a high rate of adherence of CPT [33]. Five studies reported that positive perception of CPT were associated with higher adherence to CPT [26, 27, 30, 32, 35]. Two studies reported that greater self-efficacy was an independent predictor of adherence [27, 35]. A high annual household income (more than $50,000), maternal college education, and more adults in the household were associated with higher adherence rate to CPT [34, 36].

3.5 Barriers to adherence of CPT

The lack of time was the commonest reason for not performing CPT [19, 32, 33]. The other reasons were competing priorities, heightened awareness of disease trajectory, privacy concerns, and lack of perceived consequences from non-adherence [32].

Table 3: Methods, definition, rate and outcomes of adherence to CPT.

4. Discussion

The management of NCFB is challenging with a major focus on pharmacological interventions. Pharmacological interventions are often expensive, have undesirable side effects, and are potentially time consuming such as nebulisation therapies. However, non-pharmacological interventions such as CPT, provides independent application, allows patients to have full control over the therapy, has no side effects and is often easy to use. However, to yield desirable effects, CPT needs to be performed on a long-term basis with patient’s adherence to treatment, motivation and the understanding of the benefits.

From our systemic review, we observed that higher adherence rate to CPT were associated with the paediatric population, higher treatment burden, the use of a flutter device, perception of the importance of CPT, higher annual household income, and the maternal education level of the affected child. There are two potential explanations for the higher rate of adherence to CPT in the paediatric population. Firstly, parents who strongly believe in the efficacy of CPT are more likely to ensure their children adhere to CPT [30]. Secondly, the adherence to CPT is also dependent on the assistance and support from the parents and carers. This is especially true for children of younger age as they can neither comprehend the benefits of CPT nor can they perform CPT independently.

Patients with more severe underlying respiratory diseases have a higher burden of treatment. They tend to have more symptoms and hence, lower QoL than patients with lower burden of treatment. Patients with more severe lung disease are more likely to adhere to their treatment regime [24, 25]. It is noteworthy that the overall QoL will improve with regular treatment of airway clearance. Two studies reported the adherence of CPT on CPT modalities [19, 34]. Flutter device was found to have a higher rate of adherence than other CPT modalities such as HFCWO, percussion and postural drainage, or PEP devices. The flutter device is easily mastered, portable and enables self- treatment thereby increasing adherence [34].

Mikesell and co-workers reported fewer pulmonary exacerbations among patients who had greater rate of adherence of CPT [31]. However, it is contrary to another report which did not find any significant difference in pulmonary exacerbation between the adherent and non-adherent group [24]. This may be explained by the differences in disease severity, the differences in duration of CPT, and the treatment modality used in these two studies. These two studies were unable to discern the direction of the relationship between adherence and pulmonary exacerbation.

The recognition of the necessity of CPT plays an important role in determining adherence. Goodfellow and co-workers used a multi-method approach assessment on adherence of treatment in children with CF [30]. They found out that children whose parents strongly believe in the treatment and children of younger age were significant independent predictors of the child’s adherence to CPT [30]. It is therefore important for the physicians to iterate the importance of CPT to the patients and carers, and to cultivate a strong belief in the treatment.

The time pressure is the commonest barrier for adherence to CPT [19]. To encourage adherence, treatment regime tailored to the needs and characteristics of the patients should be simple and not time-consuming. Additionally, CPT modalities that involve the use of devices (e.g. Acapella) should be considered as it improves mobilisation of mucus from airways, resulting in a shorter therapy session.

An important shortcoming of this review is small sample size with short duration of the studies which may not be enough to determine the effectiveness of the CPT on clinical outcomes. Follow up studies with bigger study populations over longer periods may overcome this limitation, and likely provide additional and important information on factors that may predict adherence of the CPT and its efficacy on treatment of bronchiectasis. The development of an ideal novel CPT device should focus on easy accessibility, usability, self-treatment and enabling treatment response monitoring.

5. Conclusion

In summary, our systemic review demonstrated that adherence to CPT is associated with reduction in pulmonary exacerbations and hospitalisations. A higher annual household income, perception on the importance of CPT, and higher education level of carers are predictors of adherence of CPT. The time pressure is the main barrier to the adherence of CPT. In addition, the lack of knowledge on of CPT on NCFB is significant especially with an anticipated worldwide increase of the prevalence NCFB. There is a greater need for better understanding of the clinical consequences and economic impact of CPT on patients with NCFB.

Acknowledgements

We thank Ms. Sandra Lawton and Dr. Priyanka Prasad for proof reading the manuscript.

Conflict of Interest

All the authors declare that they have no financial and no competing interests.

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