Patients with idiopathic pulmonary fibrosis (IPF) tend to have a high prevalence of multimorbidity, with arterial hypertension, gastroesophageal reflux disease (GERD), hypercholesterolemia, emphysema, and obstructive sleep apnea being the most common comorbidities in this population, according to study findings published in Respiratory Medicine. Study investigators identified 4 distinct comorbidity clusters that could represent IPF phenotypes.

To gauge the real-world prevalence of multimorbidity in the IPF population, researchers from Denmark examined 150 adult patients with IPF (mean age, 72.9 years; 81.3% male) from 3 tertiary Danish interstitial lung disease referral centers. To assess comorbidities, the investigators evaluated medical history, medication use, and several measures for pulmonary and cardiovascular status, exercise capacity, obstructive sleep apnea, endocrine status, and other conditions. Blood samples were also obtained to test hematologic, endocrine, renal, inflammatory, and liver status. The researchers used self-organizing maps to identify comorbidity clusters and characterize phenotypes.

In regard to the number of comorbidities, all but 1 patient had at least 1 comorbidity. Additionally, over half of the patient population had at least 6 comorbidities, indicating a high prevalence of multimorbidity. At baseline, the most prevalent comorbidities present in more than15% of patients were arterial hypertension (>60%), GERD (>40%), hypercholesterolemia (>40%), emphysema (>40%), obstructive sleep apnea (>40%), and ischemic heart disease (>20%), among several others.

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The investigators identified 4 comorbidity clusters, each with significantly different and distinct comorbidity profiles, patient characteristics, symptom burdens, and disease severity.

In cluster 1 (n=43), patients had significantly fewer comorbidities than patients in clusters 2, 3, and 4 (mean, 6.4 vs 13.7, 10.6, and 17.7, respectively; P <.05). More patients in cluster 1 were also never smokers, and fewer patients in this cluster were on long-term oxygen therapy and had a lower body mass index compared with the other clusters. Patients in cluster 1 also had less advanced disease and better health-related quality of life (HRQoL) in regard to dyspnea.

In cluster 2 (n=50), patients more often had ischemic heart disease than patients in clusters 1, 3, and 4 (54.0% vs 4.7%, 2.6%, and 36.8%, respectively; P <.05) as well as arterial hypertension (78.0% vs 44.2%, 55.3%, and 73.7%, respectively; P <.05), hypercholesterolemia (96.0% vs 4.7%, 15.8%, and 63.2%, respectively; P <.05), diabetes mellitus (40.0% vs 7.0%, 7.9%, and 21.1%, respectively; P <.05), chronic kidney disease (28.0 vs 4.7%, 23.7%, and 10.5%, respectively; P <.05), and obstructive sleep apnea (56.0% vs 46.5%, 18.4%, and 42.1%, respectively; P <.05). Patients in this cluster were older than average, compared with the other cohorts, and were mostly male.

In cluster 3 (n=38), patients more often had emphysema than patients in clusters 1, 2, and 4 (86.8% vs 2.3%, 36.0%, and 68.4%, respectively; P <.05) as well as airway obstruction (36.8% vs 0%, 10%.0, and 21.1%, respectively; P <.05). Cluster 3 also had a better HRQoL in regard to less psychological distress.

Patients in cluster 4 (n=19) more often had anxiety than patients in clusters 1, 2, and 3 (84.2% vs 7.0%, 6.0%, and 7.9%, respectively; P <.05), as well as depression (94.7% vs 9.3%, 12.0 and 10.5%, respectively; P <.05), pain disorders (52.6% vs 9.3%, 14.0%, and 36.8%, respectively; P <.05), GERD (78.9% vs 34.9%, 46.0%, and 44.7%, respectively; P <.05), emphysema (68.4% vs 2.3%, 36.0%, and 86.8%, respectively ; P <.05), and a greater total number of comorbidities (mean, 17.7 vs 6.4, 13.7, and 10.6, respectively; P <.05).

Most patients in cluster 4 were former smokers and had higher disease severity in terms of lower diffusing capacity of the lung for carbon monoxide and lower exercise capacity. Cluster 4 also demonstrated more dyspnea and psychological distress compared with the other clusters.

No significant differences were identified between clusters in terms of mortality. All patients except for those in cluster 4 had an annual reduction in HRQoL.

Limitations of this study included the small number of patients in the individual clusters as well as the reliance on some patient-reported comorbidities.

With these findings, said researchers, “increased knowledge of comorbidities will facilitate interventions aimed at prevention and treatment of comorbidities in patients with IPF.”

Disclosure: This clinical trial was supported by Boehringer Ingelheim Denmark. Multiple authors declared affiliations with the pharmaceutical industry. Please refer to the original article for a full list of disclosures.


Prior TS, Hoyer N, Hilberg O, et al. Clusters of comorbidities in idiopathic pulmonary fibrosis. Respir Med. 2021;185:106490. doi:10.1016/j.rmed.2021.106490