Idiopathic Pulmonary Fibrosis (IPF)


Idiopathic pulmonary fibrosis (IPF) is a progressive, interstitial lung disease with a poor prognosis. The median survival for untreated patients is 3 to 5 years after diagnosis.1 The most common symptoms include exertional dyspnea and chronic cough but may also include ‘finger clubbing’ and bibasilar inspiratory crackles.2 A number of different comorbid diseases may also be present in patients, which can affect prognosis and lead to treatment difficulties.1 The exact reason these comorbidities appear more prevalent in patients with IPF than the general population is unknown, however, it may be related to their overlap in risk factors such as age and smoking.3

GERD

Gastroesophageal reflux disease (GERD) is a common comorbidity found in IPF patients. Some studies have estimated its prevalence at 30%-50% of IPF patients, but many patients may be asymptomatic.4 Studies utilizing esophageal pH probes indicated that the prevalence may actually be more than 80% of patients.4 Some researchers hypothesize that GERD may be a contributing factor to IPF pathogenesis and progression through aspirations and microaspirations of gastric contents.5 Because of this potential risk, treatment guidelines presented by the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society (ATS/ERS/JRS/ALAT) recommend the use of antacids, including histamine-2 blocker receptor antagonists and proton pump inhibitors, for IPF patients.6

Emphysema

Roughly 30% of IPF patients also have pulmonary emphysema, which is most likely related to the fact that 70% to 80% of IPF patients report a history of smoking.4 The combination of pulmonary fibrosis and emphysema (CPFE) appears to be more prevalent in male patients with an extensive history of smoking and an increased requirement for supplemental oxygen and may represent a unique phenotype of IPF.4 It is unclear whether the 2 conditions increase the risk of one another or are simply concurrent due to overlapping risk factors such as smoking.3 Patients with CPFE may be at a higher risk of pulmonary hypertension or lung cancer, as well.3

Pulmonary Hypertension

Patients with IPF may also experience pulmonary hypertension, defined as mean pulmonary arterial pressure ≥ 25 mmHg.7 The prevalence of PH is variable for IPF patients and may be related to the severity of the disease, with mild cases having a reported range of 8% to 17% while more advanced patients on the lung transplant list reported a range of 30% to 50%.3 Patients can be screened for PH by looking for oxygen desaturation, dyspnea, and diffusion capacity of the lung for carbon monoxide (DLCO) that are disproportionate for the level of pulmonary function as well as evidence of right heart failure, enlargement of the right pulmonary artery, or hypertrophy of the right ventricle.4 Vasodilators have not been shown to be effective in the treatment of PH in the past but supplemental oxygen and diuresis may help alleviate some symptoms.3

Lung Cancer

Lung cancer is another comorbid lung disease that is more prevalent in IPF patients. Patients have an estimated 5- to 7-fold increase in risk compared to the general population.3-4 Although the reason for the increased risk is unknown, several risk factors likely contribute to the increase including age, male sex, and a history of smoking.3 Studies have found that squamous cell carcinomas may be slightly more common than adenocarcinomas.4 Treatment of lung cancer in IPF patients may be challenging, as common methods such as surgical removal, chemotherapy, and radiation may increase the risk of acute exacerbations and rapid deterioration.4 

Cardiovascular Disease

Several forms of cardiovascular disease, including coronary artery disease (CAD), congestive heart failure, and atrial fibrillation, have also been associated with IPF patients.3 CAD has an estimated prevalence between 4% and 25% in IPF patients.4 Comorbid cardiovascular disease is most likely due to the overlap in risk factors between the diseases, including male gender, advanced age, and history of smoking.4

Sleep Disordered Breathing

Sleep quality may also be affected in IPF patients. Patients may experience nocturnal cough, hypoxemia, and obstructive sleep apnea (OSA), which can lead to fatigue and low energy levels.3 OSA may be present in 58% to 88% of IPF patients and may be associated with ischemic heart disease.4 Nocturnal hypoxemia has also been shown to predict higher mortality and may also reflect PH.4 OSA should be treated with continuous positive airway pressure (CPAP) to improve quality of life.4

Diabetes mellitus

Several case-control studies found significantly higher rates of type 2 diabetes mellitus in IPF patients compared to matched controls. The estimated prevalence ranged from 10% to 33% of IPF patients.4

Hiatal Hernia

Studies have estimated hiatal hernia rates of 40% to 53% in IPF patients. The rate of hiatal hernia may contribute to the rates of GERD seen in IPF patients as well. Hiatal hernias can be identified on mediastinal high-resolution computed tomography (HRCT) scans being performed as part of IPF diagnosis and does not necessarily require separate imaging. Hernia-associated GERD can be treated with antacids but corrective surgery may be required in some patients.4

Hypothyroidism

Hypothyroidism may also be found in higher prevalence in IPF patients than in the general population. It is estimated that 13% of men and 28% of women with IPF have hypothyroidism, compared to 1% to 2% of men and 5 to 9% of women in the general population. The exact cause of these 2 comorbid conditions is unknown but aberrant immune activity could contribute to both.4

Mental Health

Depression and anxiety are also frequent comorbid conditions with IPF patients with prevalence estimates ranging from 20% to 50%.3 Depression and anxiety may be linked to dyspnea as dyspnea can increase distress while depression and anxiety may increase the perception of dyspnea.3 Increasing duration of the disease and higher numbers of comorbid conditions may also increase the risk of depression and anxiety in IPF patients.4 Poor levels of sleep have also been associated with depression.3 Antidepressants or cognitive behavioral therapy may help with the treatment of these conditions in some patients.3 Pulmonary rehabilitation and participation in IPF support groups may also help improve mood.3

References

  1. Quinn C, Wisse A, Manns ST. Clinical course and management of idiopathic pulmonary fibrosis. Multidiscip Respir Med. 2019;14(1):35.
  2. Nakamura Y, Suda T. Idiopathic pulmonary fibrosis: diagnosis and clinical manifestations. Clin Med Insights Circ Respir Pulm Med. 2015;9(Suppl 1):163-171.
  3. Rozenberg D, Sitzer N, Porter S, et al. Idiopathic pulmonary fibrosis: a review of disease, pharmacological, and nonpharmacological strategies with a focus on symptoms, function, and health-related quality of life. J Pain Symptom Manage. 2020;59(6):1362-1378.
  4. Oldham JM, Collard HR. Comorbid conditions in idiopathic pulmonary fibrosis: recognition and management. Front Med (Lausanne). 2017;4:123.
  5. Spagnolo P, Tzouvelekis A, Bonella F. The management of patients with idiopathic pulmonary fibrosis. Front Med (Lausanne). 2018;5. doi:10.3389/fmed.2018.00148
  6. Raghu G, Rochwerg B, Zhang Y, et al. An official ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis. An update of the 2011 clinical practice guideline. Am J Respir Crit Care Med. 2015;192(2):e3-19.
  7. Sgalla G, Iovene B, Calvello M, Ori M, Varone F, Richeldi L. Idiopathic pulmonary fibrosis: pathogenesis and management. Respir Res. 2018;19(1):32.

Reviewed by Harshi Dhingra, MD, on 7/1/2021.

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