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Researchers Identify Patients With COPD at Risk for Hypercapnia Development


Researchers analyzed 2 cohorts of patients with chronic obstructive pulmonary disease (COPD) to characterize who is most at risk for developing hypercapnia and who could most benefit from at-home noninvasive inhalation therapy.

Patients with chronic obstructive pulmonary disease (COPD) who have a lower lung function and a prior history of acidotic hypercapnic respiratory failure (AHRF) are more likely to develop hypercapnia, which can lead to disease worsening over time, according to a recent study.

The researchers, whose results were published in the Canadian Respiratory Journal, said that, “Identification of patients who are likely to become hypercapnic, or to develop AHRF, is important in COPD if we are to avoid the deleterious consequences of hospital admission and select patients for use of home NIV [noninvasive ventilation] in a timely manner.”

Hypercapnia and AHRF can be markers for poor prognosis, with only about 50% of patients with AHRF living past 1 year after diagnosis. In the United Kingdom, 35% of all COPD hospitalizations have respiratory failure and 44% had elevated CO2 contents in the blood (PaCO2), suggesting that AHRF is common among patients with COPD.

NIV in an effective treatment option that is commonly used in hospitalized patients with severe COPD. NIV is also available for use as a nightly at-home treatment to manage chronic respiratory failure in patients with COPD. Patients with persistent hypercapnia benefit the most from home NIV therapy.

“With the advent of home NIV as a treatment proven to reduce mortality and hospital admissions in COPD, it is possible that prognosis will continue to improve, but only if these high- risk patients are identified early for treatment,” wrote the investigators.

Investigators hypothesized that inadequate characterization may be the prime reason that previous research has not been able to design an effective predictive model for hypercapnia. They studied 2 cohorts of patients with COPD to identify patients predisposed to hypercapnia.

The first cohort included patients with a homogenous phenotype for COPD (usual COPD) and patients with an alpha 1 antitrypsin deficiency (AATD), a genetic disorder associated with COPD onset, sampled from 4 previously established UK cohorts. The second was a newly recruited cohort that was evaluated using a sleep study and a 1-year follow-up, recruited from the University Hospitals Birmingham NHS Foundation Trust between August 2014 and August 2015.

The COPD phenotype cohort included 1224 total patients, 637 of whom had usual COPD and 587 with AATD. The mean age of the patients was 74 years and 56.4% were women. Patients with usual COPD had a much higher hypercapnia prevalence than patients with AATD (P < .01) and were 14.82 (95% CI, 6.67-32.92; P < .01) times more likely to be hypercapnic after investigators regressively adjusted for baseline differences.

Additionally, patients with usual COPD had a significant association between hypercapnia and reduced forced expiratory volume (FEV1), long-term oxygen therapy (LTOT), lower partial pressure of oxygen, higher bicarbonate levels, and base excess in the blood.

The multivariate analysis identified FEV1 and current use of LTOT as independent predictors of hypercapnia in COPD, which explained 11% of the variance in CO2 contents in the blood. Hypercapnia risk was doubled for every 1 kPa (7.5 mmHg) lower PaO2 (odds ratio [OR], 2.05; 95% CI, 1.23-3.33; P <.01) and current smoking status attributed to a OR of 9.69 (95% CI, 2.85-33.08, P < .01), which together accounted for 28% of the variance observed.

Mortality was not influenced by hypercapnia within the usual COPD group. However, patients were 1.65 (95% CI, 1.06-2.56; P = .03) times more likely to die if their PaCO2 was increasing.

There were 160 patients in the sleep study cohort: 94 did not have a history of AHRF and 66 required NIV for AHRF management during a previous hospital admission. Current smokers accounted for 21%. Comorbidities, including hypertension (41%), documented vascular disease (20%), and osteoporosis (10%), were common.

In total, 44 patients had sleep disordered breathing, among whom 17 had obstructive sleep apnea hypopnea syndrome. All were offered continuous positive airway pressure therapy. There was a higher hypercapnia prevalence in both patient groups and baseline hypercapnia was significantly associated with death at 1 year.


Dave C, Wharton S, Mukherjee R, Faqihi BM, Stockley RA, Turner, AM. Development and relevance of hypercapnia in COPD. Can Respir J. Published online February 22, 2021. doi:10.1155/2021/6623093

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