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. Author manuscript; available in PMC: 2020 May 11.
Published in final edited form as: Arch Pathol Lab Med. 2012 May;136(5):470. doi: 10.5858/arpa.2011-0650-LE

Is Obstructive Sleep Apnea a Cause of Idiopathic Pulmonary Fibrosis?

DAVID J LEDERER 1,2, SANJA JELIC 3, ROBERT C BASNER 4, JAHAR BHATTACHARYA 5
PMCID: PMC7213593  NIHMSID: NIHMS1584657  PMID: 22540293

To the Editor.—

We read with pleasure Dr Leslie’s thoughtful article describing a potential role for peripheral tractional lung injury in idiopathic pulmonary fibrosis (IPF).1 Mechanical stretch is a well-known cause of acute lung injury during positive-pressure ventilation,2 and the author makes a strong case for the role of alveolar stretch as a cause of alveolar injury in IPF. Notably missing from the paper, however, are postulated causes of tractional stress in the lung that could lead to IPF in susceptible individuals.

Work from our group3 and others4 suggests that obstructive sleep apnea (OSA) might be a cause of subclinical lung injury, as evidenced by elevated circulating markers of alveolar injury. In addition, animal work suggests that inspiratory resistive loading (similar obstructive hypopnea) can cause alveolar injury.5 OSA is characterized by repetitive forced inspirations against a closed glottis (Müller maneuver) that are likely to cause major decreases in lung interstitial pressures,6 resulting in alveolar deformation7 and proinflammatory capillary responses,8 including stress failure.9 Such a pattern repeated multiple times each night for decades fits the hypothesis described by Dr Leslie. Indeed, OSA and IPF share similar demographic patterns, and OSA has been found to be prevalent in IPF.10

In addition to tractional injury, OSA could further injure the lung through oxidative stress (due to cyclic hypoxia-reoxygenation during recurrent apneas), through hypercapnic microRNA induction,11 and perhaps through microaspiration due to gastroesophageal reflux (GER), a condition common to both IPF and OSA. Alternatively, the reported link between GER and IPF might be completely confounded by OSA.

Additional work is required to confirm that OSA is indeed a cause of alveolar injury in humans. An important step will be determining whether OSA treatment can slow or even reverse lung fibrosis in adults with IPF. Congratulations to Dr Leslie for developing a specific, detailed, and plausible hypothesis for the cause of this devastating and underinvestigated disease.

Contributor Information

DAVID J. LEDERER, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032.

SANJA JELIC, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032.

ROBERT C. BASNER, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032.

JAHAR BHATTACHARYA, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032.

References

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