Comorbiditiy Management

PATIENTS WITH IPF OFTEN HAVE 1 OR MORE COMORBIDITIES^1,2

• Pulmonary hypertension (PH)
• Emphysema
• Lung Cancer
• Gastroesophageal reflux disease (GERD)
• Coronary artery disease (CAD)
• Sleep apnea

PULMONARY HYPERTENSION

PATIENTS WITH IPF HAVE A SIGNIFICANTLY INCREASED RISK FOR PULMONARY HYPERTENSION.^a,1

Patients with IPF and PH have an increased 1-year mortality rate compared with patients without PH.³

IPF+PH: 29%

IPF only 6%

P=0.002

PULMONARY HYPERTENSION REDUCES HEALTH STATUS FOR PATIENTS WITH IPF.

Combined IPF and PH is associated with:^3,4

• Low diffusing capacity for carbon monoxide (DLco)
• Shorter walk distances
• Desaturation during exercise
• An increased risk of death

Symptoms of PH in patients with IPF may be nonspecific.⁵

PRESENCE AND SEVERITY OF PH AFFECTS SURVIVAL TIME OF PATIENTS WITH IPF.⁶

Median survival (%) in patients with IPF and PH (95% CI):⁶

1-year survival

• ≤35mm Hg (n=14): 100
• 36-50 mm Hg (n=47): 79
• >50mm Hg (n=27): 44

3-year survival

• ≤35mm Hg (n=14): 64
• 36-50 mm Hg (n=47): 61
• >50mm Hg (n=27): 32

No PH: mean pulmonary artery pressure <25 mmHg

PH: mean pulmonary artery pressure ≥25 mmHg

TREATING COMORBIDITIES IN IPF MAY OR MAY NOT INFLUENCE CLINICAL OUTCOMES.

There is no recommendation for or against treating PH in patients with IPF at this time⁷

EMPHYSEMA

PATIENTS WITH IPF HAVE A SIGNIFICANT RISK OF HAVING CONCOMITANT EMPHYSEMA.

Patients with combined IPF and emphysema (CPFE) have more severe outcomes than patients with IPF alone.^8,9 Risk factors include male gender and smoking.⁸

In small studies, the reported prevalence of CPFE is ~28%-43%.^8,9

PATIENTS WITH CPFE HAVE MORE SEVERE OUTCOMES THAN PATIENTS WITH IPF ALONE.

A single-institution cohort of patients with IPF diagnosed between 1996 and 2006 found that emphysema produced a hazard ratio (HR) of 1.99 (P=0.02) for mortality.⁸

THE PRESENCE OF PH CORRESPONDS WITH HIGHER MORTALITY IN PATIENTS WITH CPFE.

Severe PH associated with emphysema may contribute to the higher mortality rate in patients with CPFE in this subgroup of patients.⁹

CPFE: Example

Conserved spirometry and lung volumes with diminished diffusing capacity may suggest the presence of CPFE.^10-12

Images courtesy of and used with permission from Kevin Flaherty, MD.

CPFE HAS A DIFFERENT PULMONARY FUNCTION TEST (PFT) PROFILE THAN IPF ALONE.¹⁰

FEV₁

• IPF: 85%
• CPFE: 89%

FVC

• IPF: 73%
• CPFE: 107%

FEV₁/FVC

• IPF: 86%
• CPFE: 61%

DL_CO

• IPF: 66%
• CPFE: 33%

TREATING CPFE

There are currently no evidence-based recommendations for treating emphysema in patients with IPF.¹³

LUNG CANCER

LUNG CANCER IS FOUND AT HIGHER RATES IN PATIENTS WITH IPF THAN IN CONTROLS.

• Several studies have shown a higher incidence of lung cancer in patients with IPF^1,2,14,15
• Incidence of lung cancer is even higher in patients with CPFE than those with IPF alone¹⁶

THE CUMULATIVE INCIDENCE OF LUNG CANCER IN PATIENTS WITH IPF INCREASES OVER TIME.

Out of 103 patients with IPF at a single center, 15% developed lung cancer by 5 years postdiagnosis.¹⁴

TREATING LUNG CANCER

The US Preventive Services Task Force (USPSTF) recommends annual lung cancer screening for people ages 55-80 with a 30-pack-year history and currently smoke or have quit in the past 15 years.¹⁷

There is no recommendation for routine lung cancer screening specifically for patients with IPF.¹³

GASTROESOPHAGEAL REFLUX DISEASE

GERD IS A COMMON COMORBIDITY IN PATIENTS WITH IPF.

GERD is considered a risk factor for IPF¹³, although the role of chronic microaspiration in IPF pathogenesis or disease progression is poorly understood.^18,19

As many as 94% of patients with IPF may have GERD.^20,21

SEVERAL STUDIES HAVE SHOWN AN INCREASED PREVALENCE OF GERD IN PATIENTS WITH IPF.^18,20-21

Approximately 50% of all cases of GERD in IPF are asymptomatic, making it difficult to diagnose GERD by symptoms alone.^18,21-22 Esophageal monitoring may offer a more accurate diagnosis of GERD.^23,24

TREATING GERD

The ATS/ ERS/JRS/ALAT guidelines provide a conditional recommendation for the use of antacids for treating GERD.⁷

The need for GERD treatment should be evaluated on a case-by-case basis.

Adapted from Lee JS et al. Am J Respir Crit Care Med. 2011;184(12):1390-1394.

CORONARY ARTERY DISEASE

UP TO 25% OF PATIENTS WITH IPF MAY HAVE UNDERLYING CORONARY ARTERY DISEASE.¹

In a study of 18,572 patients with IPF and their age- and gender-matched controls, CAD was significantly more common in patients with IPF.¹

HRCT CAN BE USED TO SCREEN FOR CAD IN PATIENTS WITH IPF.

A single-institution study found that HRCT could predict underlying moderate to severe CAD in 57 patients with IPF who received left heart catheterization (LHC) during evaluation for lung transplant.²⁵

^bNonsignificant CAD ≤50% occlusion of major vessel or disease of smaller vessels.

^cSignificant CAD = need for an intervention or major vessel with >50% lesion.

Table adapted from Nathan SD et al. Respirology. 2011;16(3):481-486.²⁵

LHC, left heart catheterization.

PRESENCE OF SIGNIFICANT CAD REDUCES OVERALL SURVIVAL IN PATIENTS WITH IPF.

In a single-institution study, significant CAD was correlated with mortality (HR=4.5) in a group of patients with IPF (n=73) or COPD (n=56).²⁶

OBSTRUCTIVE SLEEP APNEA

IPF OFTEN DISRUPTS PATIENTS’ SLEEP.

• Sleep disturbance may result from coughing and nocturnal hypoxia²⁷

Sleep disturbance from coughing contributes to increased daytime sleepiness in patients with IPF²⁷

OBSTRUCTIVE SLEEP APNEA (OSA) IS COMMON IN PATIENTS WITH CHRONIC LUNG DISEASES.¹³

In a single-center study, 50 patients with IPF underwent nocturnal polysomnography (NPSG) to evaluate the prevalence of obstructive sleep apnea in IPF.²⁸

Most patients with IPF have moderate to severe OSA:

• Moderate to severe: 68%
• Mild: 20%
• None: 12%

No OSA (apnea-hypopnea index (AHI) 0-5 events/h).

Mild OSA (5.1-15 events/h).

Moderate-to-severe OSA (AHI >15 events/h).

TREATING OSA

There are currently no evidence-based recommendations for treatment of sleep-related breathing disorders in patients with IPF.¹³

^aCompared to age- and gender-matched controls.

REFERENCES