Interstitial Lung Disease (ILD)

– Refers to a spectrum of pulmonary diseases that primarily affect the gas exchange capacity of the lungs. In general, diseases of the airways and pulmonary vasculature are excluded from this classification.

ILDs are also referred to as:

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– Diffuse parenchymal lung diseases

– Pulmonary fibrosis

– Chronic infiltrative lung diseases

The differential diagnosis of ILDs is quite lengthy, but can be generally divided into idiopathic entities and those associated with specific causes:

Idiopathic Interstitial Pneumonias

Idiopathic pulmonary fibrosis (IPF)

Nonspecific interstitial pneumonia (NSIP)

Acute interstitial pneumonia (AIP)

Desquamative interstitial pneumonia (DIP)

Cryptogenic organizing pneumonia (COP)

Specific Causes

Hypersensitivity pneumonitis

Drug-induced lung disease

Connective tissue disease-associated ILD

Lymphangitic carcinomatosis

1. Description of the problem

Acute respiratory failure, while associated with significant morbidity and mortality in all affected patients, can be particularly challenging and devastating in patients with underlying ILD, whose respiratory reserve may be quite limited.

The differential diagnosis and etiology of acute respiratory failure in individuals with ILD is broad and includes:

– Infection, particularly pneumonia, both opportunistic as well as community-acquired and hospital-acquired. Acute lung injury from sepsis of non-pulmonary etiology can also occur.

– Left heart failure

– Thromboembolic disease

– Pneumothorax

– Acute exacerbations of ILD: Defined as acute clinical deterioration (over <30 days) without an identifiable cause, and accompanied by new or increased bilateral radiographic infiltrates, and worsening hypoxemia in patients with ILD. This is well recognized and best described in patients with IPF, but can occur in other fibrotic lung conditions. Acute exacerbation of ILD remains a diagnosis of exclusion, most appropriately made after infection, left heart failure, and other etiologies have been confidently excluded. The incidence of acute exacerbations of IPF has been reported to be as high as 15-20%.

– Miscellaneous: drug-induced pulmonary toxicity, diffuse alveolar hemorrhage

Clinical features

Acute respiratory failure may be characterized by:


– worsening dyspnea

– cough

– sputum production

– chest pain

– fever

– hemoptysis

– altered mental status: confusion/delirium, somnolence


– localizing findings on physical examination to suggest infection, volume overload, pneumothorax, DVT

– new or worsening hypoxemia and/or hypercapnia

– cyanosis

– new or worsening radiographic infiltrates

Key management points

In determining the emergent and subsequent management of these patients:

– Start with the ABCs:

– – assess vital signs, including hemodynamic status, respiratory rate and oxygenation (SpO2)

– – evaluate for overt signs of impending respiratory collapse, including paradoxical breathing pattern

– – obtain arterial blood gases

– Stabilize the patient:

– – administer supplemental oxygen and perhaps mechanical ventilation, to optimize arterial oxygenation

– – obtain intravenous access

– – provide hemodynamic support as necessary

– Proceed with initial work-up to identify acute and potentially rapidly reversible causes of respiratory failure:

– – chest x-ray (CXR), electrocardiogram, laboratory data

– Treat empirically for plausible etiologies:

– – antibiotics, anticoagulation, for example

– Embark on more detailed diagnostic work-up as guided by clinical history, physical examination and initial objective data

2. Emergency Management

See above.

3. Diagnosis

The diagnostic approach to acute respiratory failure in ILD, as with all patients, should include a detailed history, physical examination, and objective studies.


– elucidate symptoms to suggest a specific diagnosis such as infection/pneumonia or left heart failure

– identify risk factors for entities such as pulmonary embolism and opportunistic infection

– review list of medications. Is the patient taking immunosuppressive medications (corticosteroids, azathioprine, cyclophosphamide, etc.)? Is the patient taking a medication associated with pulmonary toxicity?

Physical exam:

– evaluate for findings to suggest volume overload, DVT, pneumonia

Objective studies:

All patients:

– Chest X-ray: this is an important first screening tool to identify potential causes such as pneumothorax and pneumonia and to help guide additional diagnostic work-up. It should be interpreted in the context of other clinical findings.

   If CXR reveals pneumothorax: treat as appropriate

   If CXR reveals new focal consolidation: consider acute infection, specifically pneumonia

   If CXR reveals diffuse infiltrates: consider volume overload, acute exacerbation of underlying ILD, diffuse infection (viral), opportunistic infection (PCP), acute lung injury from sepsis

   If CXR does not reveal new pathology: consider pulmonary embolism

– Assessment of gas exchange: pulse oximetry and arterial blood gases

– Electrocardiogram

– Routine laboratory data: CBC with differential count, complete metabolic panel

Selected patients

– CT scan of the chest: consider a contrast-enhanced CT scan to rule out pulmonary embolism. The chest CT scan has much higher sensitivity for a diffuse pulmonary process than the CXR. Chest CT imaging is almost always obtained in clinical practice.

– Echocardiogram

– Sputum, blood and urine cultures

– Viral respiratory panel

– Ventilation-perfusion lung scan

– Other laboratory data: D-dimer, B-natriuretic peptide, cardiac enzymes

– Lower and/or upper extremity Doppler ultrasound studies

– Flexible bronchoscopy with bronchial washings/lower respiratory tract sampling for infection

– Surgical lung biopsy: generally of limited utility. The predominant finding is diffuse alveolar damage accompanying underlying fibrotic lung disease.

4. Specific Treatment

The treatment of acute respiratory failure in patients with ILD has two components. The first is supportive; the second is aimed at treating identifiable underlying etiologies.

Supportive care

– Supplemental oxygen: use judicially and wean as tolerated

– Mechanical ventilation: non-invasive positive-pressure ventilation or via endotracheal intubation

– Trial of gentle diuresis, unless there is associated hypotension/hemodynamic compromise

– Broad-spectrum antibiotics: An empiric trial of antibiotics to treat the possibility of infection while additional work-up is pursued is very commonly pursued and reasonable. If the patient is immunocompromised, one should also consider empiric therapy for opportunistic infection such as PCP.

– Hemodynamic support including pressors as appropriate

– Analgesics and/or antipyretics as appropriate

– Discontinue medications that may be associated with pulmonary toxicity.

– Deintensify immunosuppression as possible in the setting of suspected or documented infection.

Specific therapy: guided by specific entities

Pneumothorax: chest tube thoracostomy

Pulmonary embolism: treat as appropriate, including systemic anticoagulation, IVC filter placement, thrombolysis

Acute exacerbation of ILD: high-dose/pulse systemic corticosteroids (500 mg to 1 gram daily for 2-3 days) +/- cytotoxic agents, systemic anticoagulation

Left heart failure: diuresis, afterload reduction, treatment for ischemic heart disease as necessary

In some patients, especially those with acute exacerbations of ILD/IPF, lung transplantation may be a consideration.

5. Disease monitoring, follow-up and disposition

Expected response to treatment

The expected response to treatment for acute respiratory failure in this population is in part dictated by the underlying cause. In general, though, patients with ILD are likely to be slower to respond to treatment of certain conditions such as infection, given their compromised baseline respiratory status. Failure to respond to specific therapy should prompt reconsideration of the suspected diagnosis, but it must be mentioned that the treatment response rate and prognosis of respiratory failure, regardless of cause, is quite poor. Goals of care should be discussed with patients and their families.


Patients with respiratory failure and interstitial lung disease should be followed closely, including reassessment of clinical respiratory status, hemodynamics, and gas exchange. Repeat imaging and other diagnostic studies in the short term should be guided by consideration of the underlying cause, as well as the clinical course of the patient.

Once a patient has recovered from the acute illness, follow-up radiographic studies, pulmonary function tests, ambulatory pulse oximetry, etc., are helpful for ressessment of his or her respiratory status.




The overall incidence of acute respiratory failure in patients with ILD has not been well established. Infection and acute exacerbations of underlying ILD appear to be the most common precipitating etiologies. In one study of 27 patients with acute respiratory failure who underwent an extensive evaluation, infection was implicated in one third, while two thirds had a definite or suspected acute exacerbation. About three quarters of these patients required assisted ventilation. Other etiologies, including pneumothorax, thromboembolic disease, and left heart failure, are less common.


The prognosis of acute respiratory failure in patients with ILD in general, and IPF specifically, is poor, especially for those who require ICU admission and/or mechanical ventilation. In one study of patients with fibrotic lung disease including IPF, connective tissue disease-associated ILD, and drug-induced fibrosis, the hospital survival was about 37%, while the one-year survival was about 15%. In IPF patients, mortality rates of 60 to 100% have been reported.

Special considerations for nursing and allied health professionals.


What's the evidence?

Mallick, S. “Outcome of patients with idiopathic pulmonary fibrosis (IPF) ventilated in intensive care unit”. Respir Med. vol. 102. 2008. pp. 1355-1359. (This study reports the dismal prognosis of patients with IPF who develop respiratory failure.)

Stern, JB, Mal, H, Groussard, O. “Prognosis of patients with advanced idiopathic pulmonary fibrosis requiring mechanical ventilation for acute respiratory failure”. Chest. vol. 120. 2001. pp. 213-219. (This is one of the earliest reports of the poor prognosis of respiratory failure in patients with severe IPF.)

Olson, AL, Huie, TJ, Groshong, SD, Cosgrove, GP. “Acute exacerbations of fibrotic hypersensitivity pnemonitis”. Chest. vol. 134. 2008. pp. 844-850. (This is a case series reporting that acute exacerbations can occur in individuals with fibrotic hypersensitivity pneumonitis, and are associated with poor prognosis.)

Song, JW, Hong, S-B, Lim, CM, Koh, Y. “Acute exacerbations of idiopathic pulmonary fibrosis: incidence, risk factors, and outcome”. Eur Respir J. vol. 37. 2011. pp. 356-363. (This retrospective review of 461 patients reports on the one- and three-year incidence of acute exacerbations of IPF and the subsequent poor outcome.)

Huie, TJ, Olson, AL, Cosgrove, GP, Janssen, WJ. “A detailed evaluation of acute respiratory decline in patients with fibrotic lung disease: aetiology and outcomes”. Respirology. vol. 15. 2010. pp. 909-917. (This retrospective study of 27 patients assesses the causes and outcome of respiratory failure in patients with fibrotic lung diseases.)

Collard, H, Moore, BB, Flaherty, KR, Brown, KK. “Acute exacerbations of idiopathic pulmonary fibrosis”. Am J Respir Crit Care Med. vol. 176. 2007. pp. 636-643. (This review proposes diagnostic criteria for, and summarizes the current knowledge of, acute exacerbations of IPF.)