What is Interstitial Lung Disease (ILD)?

Interstitial Lung Disease (ILD) - also known as diffuse parenchymal lung disease (DPLD) - refers to a group of complex, heterogenous pulmonary disorders that collectively account for 15% of all lung disease.


ILD primarily affects the:

  • Lung interstitium (i.e. the area between the alveolar epithelium and the capillary endothelium)
  • Fibrous framework of the lung (septal and bronchovascular tissues)


 ILD is characterized by:

  • Variable levels of inflammation, fibrosis and remodelling of the pulmonary interstitium 
  • Restrictive ventilatory defect on spirometry
  • Deteriorating lung function in the face of increased respiratory effort
  • A chronic, progressive and irreversible clinical course

Classification and Causes of ILD

Due to the multifactorial pathogenesis of the 150 different subtypes of ILD, classification is often difficult and no consensus has been reached as yet.


Generally, the most simplified method of approaching ILD is to stratify its subtypes into:

  • ILD of known cause
  • Idiopathic ILD (otherwise known as Idiopathic Interstitial Pneumonia, or IIPs).


In clinical practice, some forms of ILD are more frequently encountered than others. Hence, it is important to be aware of the following more common types of ILD and consider them in your differential diagnosis of a patient with deteriorating lung function and a restrictive ventilatory defect.



      Common Subtypes of ILD to note:

      Of Special Mention: Drug-Induced ILD

      Recent research studies have found that many drugs commonly used in hospital and primary care environments also have a hand in the pathogenesis of ILD. Hence, reviewing a patient's medication history is an important step in the assessment of a patient with deteriorating lung function and no obvious underlying cause.

      Diagnostic Algorithm for ILD

       When the patient presents in clinic:

      • History - obtain the patient's account of his symptoms
      • Respiratory examination - assess the signs
      • Chest X-ray (CXR) 
      • Blood tests 
      • Other investigations


      History taking and Physical Examination - Signs and Symptoms in ILD

      A patient with ILD might present with a history of:

      • Exertional dyspnoea (ask about exercise tolerance (ET) to quantify this)
      • Paroxysmal non-productive cough
      • Tachypnoea
      • Clubbing (not always present)
      • End-inspiratory (velcro-like) crackles
      • With late-stage disease - cyanosis, type II respiratory failure, cor pulmonale

      Other possible signs and symptoms:

      • Pleurisy (RA, SLE, ankylosing spondylitis)
      • Erythema nodosum (sarcoidosis)
      • Raynaud's phenomenon (Systemic sclerosis)
      • Dry eyes and dry mouth (Sjogren's syndrome)

      Additional questions you may ask:

      • History of acid reflux - acid may irritate the lung mucosa and therefore cause a dry cough
      • Occupational history - bearing in mind asbestosis, silicosis, coal worker's pneumoconiosis, etc.
      • Exposure to birds and other potential antigens - bird fancier's lung, etc.
      • Current and previous medication history
      • Recent travel history

        NB: note the absence of wheeze or other evidence of airway obstruction to confirm restrictive pathology.

        Chest X-ray

        Look out for:

        • Solitary or multiple lung nodules - rheumatic lung disease
        • Bilateral hilar lymphadenopathy - sarcoidosis
        • Fibrotic shadowing in the upper zones - asbestosis, extrinsic allergic alveolitis, ankylosing spondylitis, radiotherapy
        • Fibrotic shadowing in the mid zone - progressive massive fibrosis (PMF)
        • Fibrotic shadowing in the lower zone - idiopathic pulmonary fibrosis, asbestosis

        Sample chest X-ray: Idiopathic Pulmonary Fibrosis

        Findings from a CXR of a patient with IPF:

        • Bibasilar reticulonodular infiltrates at both lung bases
        • Overall volume loss in both lungs
        • Poorly demarcated pleural-parenchymal borders along hemidiaphragms and cardia (i.e. parenchymal abnormalities have extended to the pleura).


        Blood tests and other investigations

        Routine baseline investigations for most patients with suspected ILD:

        • Full blood count (FBC)
        • Urea and electrolytes (U&Es)
        • Calcium - patients with sarcoidosis often have raised serum calcium levels
        • Erythrocyte sedimentation rate (ESR)
        • C-reactive protein (CRP)


        • Oxygen saturation at rest - usually <95%, due to chronic compensation
        • Lung function tests - spirometry, lung volumes and gas transfer coefficient (DLCO). FEV1/FVC >1, as it is a restrictive ventilatory defect. As the condition progresses, the patient's lung volume (and hence FVC) will decrease as respiration becomes less efficient. This decrease is often disproportionate to the decrease in FEV1 (forced expiratory volume measured in 1 second), hence making the ratio of FEV1:FVC >1.
        • Urinalysis
        • High-resolution CT (HRCT) scan to support diagnosis

        Additional tests to be performed at the clinician's discretion:

        • Serum ACE - for suspected sarcoidosis
        • Precipitating antibody to suspected antigen - for suspected hypersensitivity pneumonitis
        • Anti-nuclear cytoplasmic antibodies (ANCA) - for suspected vasculitis
        • Anti-glomerular basement membrane (anti-GBM) antibodies - Goodpasture's syndrome
        • Anti-dsDNA - SLE-related lung disease

          For some patients, a general diagnosis of ILD may be reached by this point. However, more information may be needed to reach a final diagnosis of the subtype of ILD involved, especially for the Idiopathic Interstitial Pneumonias, which are diagnosed primarily on their appearance on HRCT in combination with cytological and histological findings.

          • Bronchoscopy - to visualize the parenchyma of the lung
          • Bronchoalveolar lavage (BAL) - cytology
          • Transbronchial lung biopsy (TBLB) - histology

            Managing ILD

            ILD is usually managed according to a patient's underlying condition. In some cases, no intervention is necessary. For example, due to the high rates of spontaneous remission with mild asymptomatic lung involvement in sarcoidosis, treatment is not recommended.

            For idiopathic ILD, treatment regimens are mainly aimed at slowing the progression of the disease, as curative treatment of IIPs remains elusive. Generally, a patient will continue to experience declining lung function due to the limitations of his medical management - in some severe cases, a lung transplantation may be an option to consider.

            This section will discuss the medical management of a patient with IPF, as relevant to our case.

            Initiating the treatment of IPF

            Treatment can be initiated at presentation, or with disease progression, or alternatively only begin when the patient demonstrates moderate disease. Although this decision is up to the clinician's discretion, more doctors are beginning to treat patients upon presentation in the hopes of an improved clinical course and delayed progression to severe, debilitating respiratory limitation.

            Immunosuppressive therapy in IPF

            Although the pathogenesis of IPF is still debatable, it is commonly believed that these unexplained fibrotic parenchymal changes are secondary to the dysfunction of immunoregulatory pathways in the lung. Hence, immunosuppressive therapy - prednisolone, azathioprine and N-acetylcysteine (NAC) - is often employed as the long-term treatment regimen in a patient with IPF.

            For patients with poor tolerance of azathioprine, methotrexate and ciclosporin are possible alternatives. However, the use of methotrexate remains controversial due to its paradoxical worsening of lung fibrosis in certain patients. As a result, patients being treated with methotrexate require constant monitoring of their lung function to assess their disease states.

            Best supportive care

            As IPF remains a progressive, incurable disease, it is important to have a multifaceted, proactive approach to symptomatic treatment. This involves:

            • Oxygen therapy, with some patients requiring long-term oxygen therapy or LTOT
            • Pulmonary rehabilitation, to improve a patient's exercise tolerance (ET)
            • Opiates, for pain relief from pleurisy. NB: these drugs must be used with care, as they can cause respiratory depression if given in larger doses.
            • Antireflux therapy, with proton-pump inhibitors (PPIs) such as omeprazole
            • Withdrawal of steroids and immunosuppressants
            • Early recognition of terminal decline and liaison with palliative care specialists

            Additional recommendations for IPF:

            • Referral to high-quality clinical trials
            • Referral for lung transplantation, which is not always a viable treatment option due to the scarcity of donor organs.

            An example history: a 72 year-old man with IPF

            Understanding the History of our Patient with IPF

            1. Why is it relevant that the patient contracted pneumonia?

            Pneumonia is one of the leading causes of death in the elderly, who are generally prone to infections in the urinary tract, skin, and chest. This, compounded with the fact that he was a patient with underlying IPF and COPD, presented quite a worrying clinical picture. Due to his decreased ventilatory efficiency and history of immunosuppressive therapy with azathioprine, he was extremely susceptible to rapid clinical deterioration.

            2. How do we know that he had pneumonia?

            Although it is true that the patient did not mention any of the textbook signs suggesting pneumonia, the fact that he had underlying IPF and purulent sputum raised a high index of suspicion that he might have had a chest infection. Our patient suffered from generalized weakness, myalgia, and arthralgia which ultimately caused his repeated falls - these signs were all suggestive of an infection due to their short clinical course. As the patient had a longstanding history of IPF, it was important to consider whether he had begun to normalize any deterioration in lung function and attribute it to his condition without consulting his GP. Hence, his account of his respiratory symptoms only became comprehensive after repeated prompting, whereby it was revealed that his exercise tolerance had become severely hampered, as while he was normally able to walk about 10 yards before resting, he was now severely dyspnoeic at rest. Ultimately, the diagnosis of pneumonia was confirmed by a chest X-ray after other causes for his recurring falls were ruled out.

            3. Why did the patient have coarse crackles on auscultation instead of the fine end-inspiratory crackles that one would expect in IPF?

            Areas of fibrosis are often more prone to infection, due to the impaired function of the parenchyma in that region to clear any bacteria and residual cell debris. As a result, auscultation revealed that the infection had settled in the fibrotic regions of his lung - as coarse crackles are a sign of infection, they had been superimposed on the fine end-inspiratory crackles you would ordinarily expect to find on a patient with IPF and were thus recorded as the primary finding on auscultation in the respiratory examination.

            References and Further Reading

            1. Interstitial Lung Disease (DPLD) Guideline. British Thoracic Society. Web. .
            2. Longmore, J. M. Oxford Handbook of Clinical Medicine. Oxford: Oxford UP, 2007. Print.
            3. Chapman, Stephen. Oxford Handbook of Respiratory Medicine. Oxford: Oxford UP, 2005. Print.
            4. Robbins, Stanley L., Ramzi S. Cotran, and Vinay Kumar. Robbins and Cotran Pathologic Basis of Disease. Philadelphia: Saunders Elsevier, 2010. Print.
            5. "Interstitial Lung Disease." Interstitial Lung Disease. N.p., n.d. Web. 24 Sept. 2012. <http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/pulmonary/interstitial-lung-disease/>.

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