Preserved ratio impaired spirometry (PRISm) is a heterogeneous condition but its course and disease progression remain to be elucidated. We aimed to examine its prevalence, trajectories and prognosis in the general population.In the Rotterdam Study (population-based prospective cohort) we examined prevalence, trajectories and prognosis of subjects with normal spirometry (controls; forced expiratory volume in 1 s (FEV₁)/forced vital capacity (FVC) ≥0.7, FEV₁ ≥80%), PRISm (FEV₁/FVC ≥0.7, FEV₁ <80%) and chronic obstructive pulmonary disease (COPD) (FEV₁/FVC <0.7) at two study visits. Hazard ratios with 95% confidence intervals for mortality (until December 30, 2018) were adjusted for age, sex, body mass index, current smoking and pack-years.Of 5487 subjects (age 69.1±8.9 years; 7.1% PRISm), 1603 were re-examined after 4.5 years. Of the re-examined PRISm subjects, 15.7% transitioned to normal spirometry and 49.4% to COPD. Median lung function decline was highest in subjects with incident PRISm (FEV₁−92.8 mL·year⁻¹, interquartile range (IQR) −131.9– −65.8 mL·year⁻¹; FVC −93.3 mL·year⁻¹, IQR −159.8– −49.1 mL·year⁻¹), but similar in persistent PRISm (FEV₁−30.2 mL·year⁻¹, IQR −67.9– −7.5 mL·year⁻¹; FVC −20.1 mL·year⁻¹, IQR −47.7–21.7 mL·year⁻¹) and persistent controls (FEV₁−39.6 mL·year⁻¹, IQR −64.3–−12.7 mL·year⁻¹; FVC −20.0 mL·year⁻¹, IQR −55.4–18.8 mL·year⁻¹). Of 5459 subjects with informed consent for follow-up, 692 (12.7%) died during 9.3 years (maximum) follow-up: 10.3% of controls, 18.7% of PRISm subjects and 20.8% of COPD subjects. Relative to controls, subjects with PRISm and COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2–4 had increased all-cause mortality (PRISm: HR 1.6, 95% CI 1.2–2.0; COPD GOLD 2–4: HR 1.7, 95% CI 1.4–2.1) and cardiovascular mortality (PRISm: HR 2.8, 95% CI 1.5–5.1; COPD 2–4: HR 2.1, 95% CI 1.2–3.6). Mortality within <1 year was highest in PRISm, with patients often having cardiovascular comorbidities (heart failure or coronary heart disease; 70.0%).PRISm is associated with increased mortality and this population encompasses at least three distinct subsets: one that develops COPD during follow-up, a second with high cardiovascular burden and early mortality, and a third with persistent PRISm and normal age-related lung function decline.

Background: Increasing evidence suggests that sarcopenia and a higher systemic immune-inflammation index (SII) are linked with morbidity in patients with COPD. However, whether these two conditions contribute to all-cause mortality in middle-aged and older patients with COPD or asthma is unclear. Therefore, we investigated the association between sarcopenia, SII, COPD or asthma and all-cause mortality in a large-scale population-based setting.Methods: Between 2009 and 2014, 4482 participants (aged >55 years; 57.3% female) from the population-based Rotterdam Study were included. COPD and asthma patients were diagnosed clinically and based on spirometry. Six study groups were defined according to the presence or absence of COPD or asthma and sarcopenia. Cox regression models were used to assess all-cause mortality in the study groups, adjusted for sex, age, body mass index, SII, smoking, oral corticosteroid use and comorbidities. In addition, all participants were categorised into sex-specific quartiles of SII, and mortality in these groups was compared.Results: Over a median follow-up of 6.1 years (interquartile range 5.0–7.2 years), 466 (10.4%) persons died. Independent of the presence of sarcopenia, participants with COPD had a higher risk of all-cause mortality (hazard ratio (HR) 2.13, 95% CI 1.46–3.12 and HR 1.70, 95% CI 1.32–2.18 for those with and without sarcopenia, respectively). Compared to lower SII levels, higher SII levels increased mortality risk even in people without sarcopenia, COPD or asthma.Conclusion: Middle-aged and older people with COPD, higher SII levels or sarcopenia had an independently increased mortality risk. Our study suggests prognostic usefulness of routinely evaluating sarcopenia and SII in older people with COPD or asthma.

Increased expression of pulmonary ACE2, the SARS-CoV-2 receptor, could contribute to increased infectivity of COVID-19 in patients with diabetes, but ACE2 expression has not been studied in lung tissue of subjects with diabetes. We therefore studied ACE2 mRNA and protein expression in lung tissue samples of subjects with and without diabetes that were collected between 2002 and 2020 from patients undergoing lobectomy for lung tumors. For RT-PCR analyses, samples from 15 subjects with diabetes were compared with 91 randomly chosen control samples. For immunohistochemical staining, samples from 26 subjects with diabetes were compared with 66 randomly chosen control samples. mRNA expression of ACE2 was measured by quantitative RT-PCR. Protein levels of ACE2 were visualized by immunohistochemistry on paraffin-embedded lung tissue samples and quantified in alveolar and bronchial epithelium. Pulmonary ACE2 mRNA expression was not different between subjects with or without diabetes. In contrast, protein levels of ACE2 were significantly increased in both alveolar tissue and bronchial epithelium of patients with diabetes compared with control subjects, independent of smoking, chronic obstructive pulmonary disease, BMI, renin-angiotensin-aldosterone system inhibitor use, and other potential confounders. To conclude, we show increased bronchial and alveolar ACE2 protein expression in patients with diabetes. Further research is needed to elucidate whether upregulation of ACE2 expression in airways and lungs has consequences on infectivity and clinical outcomes of COVID-19.