Interstitial lung diseases (ILDs) are referred to as a heterogeneous entity of over 150 lung diseases that have in common to affect the connective tissue giving shape and supportive structure to the lungs (“interstitium”). This interstitium encompasses the alveolar epithelium as well as the interstitial capillaries and the surrounding soft tissue.1 Many diseases in the group of ILDs are connected to the development of pulmonary fibrosis, which might evolve also at a very late stage.1
Data on the incidence are sparse and highly variable. In general practice, ILDs account for 15 % of all respiratory diseases with 31.5 per 100,000 person-years in males and 26.1 per 100,000 person-years in females, as reported in an often cited study from New Mexico, USA.1,2
The inconsistent data of estimated incidence rates are likely to derive from different assessment procedures and diagnostic criteria and measurement.1–3
A widely accepted ILD classification scheme is based on disease causes by histopathological patterns. As a first step, this approach subdivides ILDs into forms of known and of unknown (idiopathic) causes, respectively.3 The latter account for ~ 65 % and are associated with a worse prognosis and response to therapy.1,3
Patients can easily be misclassified if medical history is considered insufficiently1. It can offer valuable clues particularly if the patient was exposed to certain hazards known to cause ILDs (see chart1).
In around 35% of these patients with ILD the disease can be linked to exogenous causes like exposition to organic or inorganic material, drug reactions and infections.
Up to 20% of ILD patients have a concomitant diagnosis of connective tissue disease like systemic sclerosis (Ssc) or rheumatoid arthritis (RA). Still, in these cases the pulmonary disease may be present months or even years ahead of systematic manifestations.
Patients with ILD associated to connective tissue disease may respond to immunosuppressive therapy and they present a better prognosis (estimated survival of 85% at 5 years) compared to patients with other ILD forms such as IPF.1,4 Therefore, all extrapulmonary symptoms as well as medical history should be assessed carefully in order to establish an appropriate diagnosis.1
Several connective tissue disorders including RA-ILD and Ssc-ILD have shown non-specific interstitial pneumonia (NSIP) to be a common pattern (see below).5,6
Most common (approx. 50%) not only among the idiopathic ILDs but ILDs in general are Sarcoidosis-associated ILD and idiopathic pulmonary fibrosis (IPF) as a subgroup of idiopathic interstitial pneumonias (IIPs).1,3
A number of gene variants have been associated with an increased risk to develop ILD disorders such as IPF and sarcoidosis.7 To date, tools and strategies are being developed to improve genetic testing for association with ILDs and to increase the resolution of gene mapping.3
Sarcoidosis is a granulomatous disease of unknown aetiology. Though not yet completely understood, there is evidence of multiple causes of sarcoidosis, each requiring a specific arrangement of antigen, human leukocyte antigen (HLA) molecule, and T-cell receptor.8
Exposure to certain agents has been suggested to be risk factors for the development of sarcoidosis as well as IPF.3
The histopathologic changes in the lungs of patients with ILD can vary considerably ranging from granulomatous inflammation without parenchymal fibrosis in patients with sarcoidosis to extensive pulmonary fibrosis with architectural distortion of the lung in patients with IPF.7
IPF usually occurs in older patients and has characteristic HRCT and lung biopsy findings. In general, IPF is characterised by more scarring and less inflammation and has a poorer prognosis than most other ILD forms.1
In contrast, NSIP is a provisional diagnosis used in cases of uncertainty, where further clarification on the nature of the corresponding clinical condition is needed. The term describes the second most common histopathological pattern in ILDs (~25% of IIPs) resulting from many different aetiologies. Despite absent histopathologic features characterising the underlying disorder, non-specific idiopathic pneumonia (NSIP) presents similarly to other idiopathic interstitial pneumonias (IIPs). NSIP pattern occurs in both ILDs with or without known cause.3,9 However, though the diagnosis of NSIP still remains one of the biggest challenges, patients with NSIP have a better prognosis than those with usual interstitial pneumonia (UIP) like IPF.1
ILD terminology and the high number of ILD varieties may be confusing, but differentiation and special attention to subtle details in radiological findings is critical as treatment response and prognosis are extremely variable.1 5 year survival rates range from 20% for idiopathic pulmonary fibrosis to almost 100% for organising pneumonia (OP).3