Effectiveness of pulmonary rehabilitation in patients with type 2 diabetes mellitus and Preserved Ratio Impaired Spirometry (PRISm)

Relevance

According to the GOLD 2025 definition, PRISm (Preserved Ratio Impaired Spirometry) is a term describing a state of lung function characterized by a reduced post-bronchodilator FEV₁ <80% of predicted, while maintaining a normal FEV₁/FVC ratio (>0.7 post-bronchodilator) [1]. Observational studies have shown that PRISm progressed to chronic obstructive pulmonary disease (COPD) in 32.6% of individuals over 4–5 years [2, 3]. The prevalence of PRISm in the general population is estimated at 7–13% [4], and it is especially common among former and current smokers. However, researchers emphasize that PRISm should not be limited to this patient cohort, since factors contributing to its development and to COPD extend beyond smoking alone (including potential effects of poor lung development, respiratory infections, occupational exposures, and air pollution) [5–8]. It has been demonstrated that PRISm may also be associated with low or high body mass, female sex, obesity, and multimorbidity [1]. The importance of diagnosing this condition lies not only in its potential progression to COPD but also in the increased risk of respiratory symptoms, hospitalizations, cardiovascular mortality, and all-cause mortality [1, 9–12]. Given that current literature lacks evidence-based management strategies for PRISm, this clinical case provides a valuable example of the potential benefits of pulmonary rehabilitation as one approach to managing patients with this type of impaired lung function.

Objective: to investigate the effectiveness of pulmonary rehabilitation in patients with type 2 diabetes mellitus (DM) and PRISm.

Materials and methods

Twenty patients with type 2 DM were examined, five of whom reported chronic cough with or without sputum production and dyspnea. The severity of dyspnea was assessed using the mMRC scale. The impact of the disease on quality of life was evaluated using the SF-36 questionnaire, which includes eight domains: physical functioning (PF), role limitations due to physical health (RP), bodily pain (BP), general health (GH), vitali­ty (VT), social functioning (SF), role limitations due to emotional problems (RE), and mental health (MH). Exercise tolerance was assessed using the 6 MWT.

All patients underwent spirometry using a portable spirometer (BTL 08 SpiroPRO) to determine the following parameters: FEV₁, FVC, VC, slow VC, and FEV₁/FVC ratio.

The pulmonary rehabilitation program included daily breathing exercises, physical activity (primarily involving the lowe­r limbs) for at least 30 minutes five times a week, and dietary thera­py.

Breathing exercises (20 minutes daily) included diaphragmatic breathing (deep abdominal breathing), Buteyko method exercises, slow exhalation through slightly pursed lips (pursed-lip breathing), and use of drainage positions. Physical activity consisted of walking, stationary cycling, squats, lunges, toe and heel raises, and light stretching after exercise.

The dietary intervention was based on the principles of a healthy plate, requiring the exclusion of high-calorie and fried foods, and reduction of salt and sugar intake. It emphasized adequate fluid intake, protein, fiber-rich foods, antioxidants, and omega-3 fatty acids.

Results and discussion

Analysis of the spirometry data showed that most patients had values above 80% of predicted. At the same time, in three patients, pre-bronchodilator testing revealed reduced FEV₁, FVC, VC, and slow VC values below 80% of predicted. However, in only one patient these values remained below 80% of predicted after bronchodilator administration, while the FEV₁/FVC ratio remained above 0.7. According to GOLD 2024, this patient could be classified as having PRISm.

Clinical Case

At the time of her 1st visit, a 54-year-old woman had been living with type 2 DM for 10 years and was receiving basal insulin glargine 34 IU in the morning in combination with metformin 1000 mg twice daily. She had never smoked but reported frequent respiratory infections over the past few years. At the time of examination, she complained of excess body weight, intermittent dry mouth, general weakness, dyspnea, and productive cough with sputum.

Physical examination indicated obesity stage 2, with a body mass index (BMI) of 39.2 kg/m². Laboratory results were as follows: fasting glucose — 10.6 mmol/L, glycated hemoglobin — 8.4%, insulin level — 5.42 μmol/L, total cholesterol — 6.8 mmol/L, triglyce­rides — 2.1 mmol/L, creatinine — 83.06 μmol/L. On the mMRC scale, dyspnea severity corresponded to grade 2.

The impact of the disease on quality of life as measured by the SF-36 questionnaire was assessed as moderate (PF — 75, RP — 50, BP — 95, GH — 55, VT — 50, SF — 90, RE — 85, MH — 65).

Cardiac auscultation revealed rhythmic, clear heart sounds. Lung auscultation revealed vesicular breath sounds. Chest X-ray findings were within age-related normal limits.

The patient was prescribed a pulmonary rehabilitation program that included daily breathing exercises, physical activity primarily involving the lower limbs for at least 30 minutes five times a week, and dietary therapy.

Another aspect of treatment involved adjusting insulin therapy by increasing the basal insulin dose to 38 IU per day and initiating statin therapy with pitavastatin 2 mg daily. Given the insufficient glycemic control and high cardiovascular risk, an SGLT2 inhibitor (empagliflozin 10 mg once daily) was also prescribed.

Due to the lack of evidence for the effectiveness of bronchodilators in PRISm, their use was not recommended. In addition, the patient was prescribed erdosteine 300 mg twice daily for 10 days. Dynamic monitoring and a follow-up visit after 4 months were also recommended.

At the time of the 2nd visit, the patient reported improved quality of life, increased physical activity, and reduced severi­ty of respiratory symptoms, specifically cough, sputum production, and dyspnea. On the mMRC scale, dyspnea severity was grade 1. According to the SF-36 questionnaire, the disease impact on quality of life decreased (PF — 80, RP — 55, BP — 95, GH — 60, VT — 60, SF — 95, RE — 90, MH — 75).

During the 6-minute walk test, the patient walked 120 m farther than at baseline. Comprehensive treatment contributed to weight loss, with BMI decreasing to 37 kg/m². Notable achievements included improved glycemic profile (fasting glucose — 8.1 mmol/L, glycated hemoglobin — 7.7%) and improved lipid profile, with total cholesterol reduced to 5.6 mmol/L and triglyce­rides to 1.7 mmol/L.

Spirometry performed during follow-up showed that despite the improvement in respiratory symptoms, there was no significant increase in spirometric parameters; however, no decline was observed either. The changes in spirometric values during treatment are shown in Fig. 1–2.

Figure 1. Spirometry values before and after bronchodilator before treatment

Figure 2. Spirometry values before and after bronchodilator after treatment

Insulin resistance, low-grade systemic inflammation, endothelial dysfunction, microvascular damage, and neurovegetative disturbances are key mechanisms of lung injury in type 2 DM. In a prospective study, 22.6% of the type 2 DM patient population had PRISm and demonstrated a significantly increased risk of nearly all adverse outcomes, including macrovascular and microvascular complications and mortality. Li G. et al. (2023) also emphasize that this patient cohort may particularly benefit from therapy intensification [13].

A strong genome-wide genetic correlation (r_g) between PRISm and spirometric COPD (r_g=0.62, p<0.001), as well as a genetic correlation with type 2 DM (r_g 0.12; p=0.007) [14], may help explain the relatively high prevalence of these comorbidities and the non-random nature of this association. On the other hand, researchers note that while a significant proportion of PRISm cases are associated with obesity, it is unlikely that obesity alone accounts for most cases. Similarly, interstitial lung diseases (ILD) can cause PRISm, but given the low prevalence of ILD, it is unlikely that they represent the majority of cases [15]. Based on clinical history and objective findings from additional diagnostic methods, ILD was excluded in our patient.

A study published in 2018 indicates that PRISm has a high rate of transition to other categories of lung function impairment and is likely composed of distinct subgroups. Therefore, it may be best identified as a window of opportunity to modify the trajectory of progressive lung function decline [3].

Referring first to normative documents (The report «Global strategy for prevention, diagnosis and management of COPD» published by the Global Initiative for Chronic Obstructive Lung Disease), we understand that there is limited reliable evidence regarding treatment of PRISm. However, the need for careful, long-term monitoring of patients is emphasized [1].

Despite the considerable limitations of the study by M.K. Han, published in 2023 in The New England Journal of Medicine, it was observed that there was no reduction in respiratory symptoms in symptomatic smokers without COPD but with preserved lung function after 12 weeks of treatment with long-acting bronchodilators (indacaterol+glycopyrrolate) compared to placebo [16]. Therefore, our knowledge remains insufficient to define a specific cohort of PRISm patients who might benefit from bronchodilator therapy.

Given that Fu X. et al. (2024), in a cross-sectional analysis of the 2024 NHANES study, concluded that a physically active lifestyle may be a potential preventive measure against PRISm [17], implementing pulmonary rehabilitation in the management of this condition may be one of the key strategies. Specifically, a higher overall level of physical activity was associated with a lower risk of PRISm among U.S. adults, especially in populations with BMI ≥25 kg/m² [17].

Other important arguments for applying pulmonary rehabili­tation in patients with type 2 DM and PRISm include prevention of sarcopenia — one of the major negative prognostic factors in COPD [18], preservation of muscle mass as a site of glucose utilization [19], potential improvement of endothelial function [20, 21], and increased antioxidant capacity of muscles [22]. Moreover, numerous studies indicate the effectiveness of both long- and short-term pulmonary rehabilitation programs in COPD [23, 24], while exercise training has long been recognized as a powerful therapeutic intervention in type 2 DM [25].

The exceptional importance of dietary modification in preventing early lung dysfunction is also supported by results of another retrospective analysis (NHANES 2007–2012) published in 2024, which investigated the association of the dietary inflammatory index and the composite dietary antioxidant index with PRISm among U.S. adults [26].

In our view, the result we obtained — preservation of spiromet­ry values without deterioration after treatment — is no less important. S.R.A. Wijnant et al. (2020), in the Rotterdam Study, confirmed that among 5,487 patients (7.1% of whom had PRISm), 1,603 underwent repeat assessment after 4.5 years. Of these, 49.4% transitioned to the COPD group, and the mean decline in lung function was greatest among subjects with incident PRISm (annual FEV₁ decline of 92.8 mL/year, interquartile range (IQR) 131.9–65.8 mL/year; FVC decline of 93.3 mL/year, IQR 159.8–49.1 mL/year). However, it is worth noting that the study also identified a subgroup with persistent PRISm, in which the annual decline in FEV₁ and FVC was 30.2 mL/year and 20.1 mL/year, respectively. On the other hand, patients with PRISm had the highest mortality rates from all causes and cardiovascular causes [2].

Conclusion

In a substantial proportion of patients with type 2 DM, PRISm remains overlooked by specialists, which may significantly worsen their health and quality of life. Implementing routine lung function testing and pulmonary rehabilitation programs in patients with type 2 DM and PRISm may be beneficial and improve disease outcomes. Further studies are needed to better recognize and subtype PRISm patients — especially those with metabolic disorders — to deepen understanding of shared pathophysiological mechanisms, identify effective strategies to improve lung function in these patients, and optimize their overall health.

References

Надійшла до редакції/Received: 07.10.2025
Прийнято до друку/Accepted: 10.10.2025

*FEV1 — forced expiratory volume in the 1st second, FVC — forced vital capacity.