Diffuse parenchymal lung diseases (DPLD) encompass over 140 different non-infectious and non-malignant diseases of the lung http://antiepileptic-meds.com/parenchyma that can basically affect all three compartments of the lung (endothelium – interstitium – epithelium) and eventually lead to increased cellularity and/or to an increased amount of connective tissue in the terminal portion of the lung. Although the prevalence of DPLD is rather rare (67.5/100,000 for females and 80.9/100,000 for males), many more patients die each year as a result of DPLD as compared to link for youasthma, which is approximately a hundred times more common. We can crudely differentiate between DPLD of known aetiology (e.g. extrinsic allergic alveolitis) and those of unknown aetiology (e.g. idiopathic interstitial pneumonia). Furthermore, it is possible to distinguish between primarily inflammatory forms (e.g. extrinsic allergic alveolitis, sarcoidosis) and forms in which the initial stage of the pathogenic sequence is chronic epithelial damage followed by an abnormal reparatory response (e.g. idiopathic pulmonary fibrosis). DPLD also occur as part of systemic connective tissue diseases (e.g. lupus), chronic inflammatory hepatic or bowel disease (e.g. Crohn’s disease) or vasculitic diseases (e.g. Wegener’s granulomatosis). Not uncommonly, medical treatments also result in DPLD being triggered (e.g. amiodarone, bleomycin). Lastly, the lung, given its large contact surface area with the environment, may be exposed to a very large number of inorganic (e.g. asbestos) or organic (e.g. fungal spores) dust particles, which can trigger DPLD.

The term DPLD which is now increasingly being used, will eventually supersede the term “interstitial lung diseases” (ILD). Moreover the terms “fibrosing lung diseases” amd “lung fibrosis” are used synonymously. In this article, we want to give an overview of all forms of DPLD with the exception of interstitial lung diseases in systemic diseases and sarcoidosis.

Despite the wide variety of underlying diseases, DPLD ultimately have many features in common: these include, firstly, the principal clinical symptom of exertional dyspnoea and later, in addition, dyspnoea at rest, the restrictive ventilatory impairment, the diffusion disorder and arterial hypoxaemia on exertion and later at rest, and finally demonstration of the typical changes on high-resolution computed tomography (HR-CT). Correct classification of the actual underlying disease requires considerable effort on the part of the patient and doctor alike and represents one of the most challenging differential diagnoses in internal medicine. It is contingent upon an appropriately thorough history, careful physical examination, lung function tests with characterisation of gas exchange at rest, complemented if necessary by stress tests (6-minute walk test, ergospirometry), serological tests, an HR-CT examination and, in most cases, bronchoscopy with bronchoalveolar lavage (BAL). Even after these procedures have been undertaken, for a considerable number of patients it is possible to narrow down the range of causes but not to clearly identify it. In these cases, depending on the patient’s age and comorbidities, an open lung biopsy (nowadays usually as minimally invasive video assisted thoracic surgery, VATS) should be attempted for a definitive clarification.

The treatment of DPLD must be directed at the primary underlying disease: in extrinsic allergic alveolitis, therefore, strict avoidance of the inhalational antigen is the most effective and most important measure. In some forms of DPLD, in which excessive nicotine abuse is believed to be an important trigger (e.g. pulmonary Langerhans cell histiocytosis, respiratory bronchiolitis ILD), the patient must be advised to categorically give up smoking or be supported in this pharmacologically. Regarding the high rate of spontaneous remissions an initial wait-and-see approach can be adopted in sarcoidosis. Pharmacologically, the treatment of ILD is still characterised by a limited range of effective drugs. Steroids are the gold standard in primary inflammatory forms of DPLD, complemented by immunosuppressant agents such as azathioprine or cyclophosphamide in order to reduce steroid toxicity. However, among the so called idiopathic interstitial pneumonias, especially in idiopathic pulmonary fibrosis (IPF) the previously recommended immunosuppressant treatment regimen revealed potentially harmful (PANTHER-IPF trial) and is no longer advisable. Novel antifibrotic drugs (pirfenidone) may bring about a reduced progression rate in some patients with mild to moderate IPF. Still, lung transplantation represents the only causal treatment option, but this also involves considerable side effects. In some forms of DPLD (e.g. sarcoidosis), pulmonary arterial hypertension (PAH), occasionally severe, may also develop over time, whilst in other forms PAH may be a prominent feature from the outset (e.g. pulmonary involvement in scleroderma). This being cause to perform initial screening procedures for PAH in every patient and to also check for this on a regular basis during the long-term course. If PAH is present, the appropriate treatment should be initiated. Experience shows that a clinically appreciable, significant treatment outcome is more likely to be achieved the greater the severity of the PAH and the less severe the degree of restriction.

In summary, the prognosis of DPLD varies enormously depending on the underlying disease and ranges from complete remission (spontaneous or on therapy), relatively stable long-term courses (spontaneous or on therapy), severe progressive forms to fulminant courses.