High-protein diet during pulmonary rehabilitation in patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a heterogeneous, progressive respiratory disease [1]. Malnutrition, including cachexia, is common [2] and is associated with reduced quality of life and exercise performance, increased gas trapping, lower diffusing capacity, peripheral muscle weakness, increased complications and mortality [3]. Pulmonary cachexia is a complex syndrome that includes reduced food intake and varying degrees of inflammation leading to anorexia, and metabolic changes including reductions in appetite sensations and elevated resting energy expenditure [4].

Supplementation of calories has shown positive effects on functional exercise capacity and quality of life [5, 6], but the effect of protein supplementation in malnourished patients remains unknown. Thus, the hypothesis of the study was that a high protein diet and exercise may improve fat-free mass (FFM), functional capacity, symptom burden and dyspnoea in malnourished COPD patients.

METHODS

Consecutive patients with severe COPD (stage III or IV [7]) who were at nutritional risk (NRS 2002, [8]) and had been referred for pulmonary rehabilitation (PR) by their general practitioner or outpatient clinic were randomised to receive dietary counselling (DC) aiming to reach a high protein diet as a supplementary component to PR or standard PR. Terminal or lung-transplanted patients and patients with severe comorbidities preventing the intervention were excluded. All participants gave informed consent. The regional ethical scientific committee and the Danish Data Protection Agency approved the protocol.

Both groups participated in the PR, which consisted of a group-based, supervised physical training with endurance and resistance training twice weekly for 12 weeks (120 min./week). The patient education sessions lasted 60-90 min. after the exercise sessions.

The intervention group (IG) received DC by experienced dieticians, aiming at a protein intake of ≥ 25 E%. An oral nutritional supplement (Atpro 200; 1,570 kJ and 92 g protein per 100 g) was used to supplement the patients’ diet to reach ≥ 25 E%/protein/day. The control group (CG) received no DC or nutritional supplementation.

The Harries and Benedict equation [9] with an individual activity and stress component was used. Dietary assessment was performed by 3 × 24-hour diet recall interviews (two weekdays and one weekend day) at baseline and at 12 weeks calculated using the Master Diætist System, Denmark® containing the Danish food composition tables.

Muscle function was assessed by the six-minute walking distance (6MWD) and handgrip strength (HGS) (Saehan DHD-1 Digital Hand Dynamometer, SH1001). FFM was measured by bio-impedance analysis (BIA) (BIA-101, RJL). Mid-upper arm circumference (MUAC) and mid-thigh circumference (MTC) were measured on the dominant side. The COPD Assessment Trial (CAT) Test [10] was used to measure global symptoms. Dyspnoea was measured by the Medical Research Council dyspnoea scale, and Borg score for perceived exertion during physical activity was measured before and after the 6MWD test [11, 12].

Compliance with the nutritional intervention was assessed by three-day 24-hour diet recall interview and return of the ATPRO 200 packages. Adherence to the PR programme was recorded.

Statistical analyses used one-way analysis of covariance (ANCOVA). In the analysis of 6MWD, gender and forced expiratory volume in the first second (FEV1) were included as covariates.

RESULTS

Among the 70 patients screened, 13 patients were randomised to intervention (n = 7) or control (n = 6). Three men from the CG withdrew their consent during the study period. Two patients were admitted to the hospital and one was lost to follow-up. Thus, ten patients were included in the analysis (Table 1).

The IG reduced 6MWD by 9.8 m and the CG by 42.5 m after 12 weeks of rehabilitation. After adjustments for gender and FEV1, the 6MWD mean group difference was 97.1 m (p = 0.04). No differences were observed between the two groups on any other endpoints (Table 2).

Compliance with the PR was 75 ± 27% (IG) and 81 ± 7% (CG). The IG increased the protein intake from 17.1 E% (1.2 g/kg/d) to 18.6 E% (1.3 g/kg/d), reaching 66 ± 23% compliance with the protein goal. The CG altered the protein intake from 13.1 E% (1.0 g/kg/day) to 12.1 E% (1.0 g/kg/day). The caloric intake of the IG was 1,752 kcal/day (94% of the requirement) at baseline and 1,755 kcal/day (87% of the requirement) at 12 weeks, whereas the CG increased their intake from 1,539 kcal/day (96% of the requirement) to 1,644 kcal/day (100% of the requirement).

DISCUSSION

Maintenance of peripheral muscle function (6MWD) was detected in the IG compared with a deterioration in the CG despite low statistical power. No group difference was detected as far as the remaining outcomes were concerned.

6MWD is a valid and reliable measure of exercise capacity in COPD patients, and a reduction is expected in these patients [13]. This correlates well with mortality risk [13] and post-operative complications [14]. Previous studies have reported conflicting results. Improved muscle endurance [15-18], muscle strength [16, 17], symptoms [16] and FFM [16, 17] have been identified. Conversely, a lack of any group effect has been reported on muscle endurance [19, 20], muscle strength [18, 20], dyspnoea [18, 19], symptoms [18-20] and FFM [19, 20]. The discrepancy in studies reporting the effect of nutritional support on physical capacity, FFM and symptoms in malnourished patients with COPD may be explained by methodological variations with respect to patients, duration, nutritional interventions, exercise elements and choice of outcome measurements [13].

The strength of the present study is the supplementation of an inexpensive protein powder to the patients’ habitual diet with a high degree of acceptance. Although the goal of at least 25 E% of protein was not reached, the IG had 40% higher protein intake than the CG after 12 weeks. The main weakness of the study was the small sample size. Conducting multiple analysis on the small sample size might have introduced type-1 error.

CONCLUSION

In patients with COPD attending rehabilitation, a high protein diet combined with physical activity had a clinically relevant effect on peripheral muscle function.

Correspondence Grith Møller. E-mail: gmp@nexs.ku.dk
Accepted 15 September 2022
Conflicts of interest none. Disclosure form provided by the author is available with the article at ugeskriftet.dk/dmj
References can be found with the article at ugeskriftet.dk/dmj
Cite this as Dan Med J 2022;69(11):A03220185