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Chronic obstructive pulmonary disease (COPD) is a chronic disease affecting millions of older adults. We investigated the prevalence of nursing home (NH) residents with COPD and their pharmacologic treatment in relation to the diagnosis of dementia and the prevalence of potentially severe drug-drug interactions (DDIs) of COPD medications with drugs prescribed to treat comorbidities. Retrospective cross-sectional multicentre study. Individuals living in long-term care NHs. This cross-sectional cohort study was conducted in a sample of Italian long-term care NHs located throughout the country. Information on drug prescriptions, diseases, and sociodemographic characteristics was collected using medical records between 2018 and 2020. Potentially severe DDIs were analyzed using INTERCheck, developed by the Istituto di Ricerche Farmacologiche Mario Negri IRCCS. Among the 2604 residents living in 27 NHs (mean age 86.4 ± 8.5 years; women 1995, 76.6%; number of drugs 7.3 ± 3.6), 306 had a diagnosis of COPD (11.8%) and 84 (27.5%) of them were treated with at least 1 medication for COPD (27.5%). Those without dementia had a higher prevalence of drugs for COPD than those with dementia (48% vs 20%, P <.0001). The most used classes for COPD were adrenergics in combination with corticosteroids (16.7%) and inhalant anticholinergics (14.7%). Among those receiving medications for COPD, 45 had at least 1 potentially severe DDI with medications for comorbidities (53.6%) and most of them were associated with an increased risk of QTc prolongation, as beta2 agonists with diuretics, antipsychotics or antidepressants. Most NH residents with COPD did not receive any medication for this disease despite the potential benefits. Residents with dementia received fewer COPD medications probably because of their compromised physical and cognitive status. One-half of the NH residents taking medication for COPD were exposed to an increased risk of QTc prolongation and torsades de pointe because of pharmacodynamic DDIs with medication for comorbidities. Close monitoring of electrocardiograms for NH residents with COPD is recommended. [ABSTRACT FROM AUTHOR]