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.

Idiopathic interstitial pneumonias (IIP), whose pathogenetic mechanisms are still largely unknown, represent a significant portion of the complex spectrum of DPLD. A classification based on histological criteria was first undertaken by Liebow and Carrington in 1969; the current classification was published in 2002 by the American Thoracic Society (ATS) and the European Respiratory Society (ERS). This latter classification is also essentially based on clinical, radiological and histopathological criteria. Overlaps between the histopathological patterns are very much a feature. If the molecular causes for the development of IIP are discovered, a further revision of this classification will be expected. Besides the defined entities of IIP described below, there is also a category called “unclassifiable interstitial pneumonia,” a term that should always be used if a clear classification (e.g. in the case of terminally altered lung tissue) is no longer possible.

IPF, also known as cryptogenic fibrosing alveolitis (CFA), occupies a special place among all forms of DPLD in that it is the condition with the worst prognosis and a generally rapidly progressive course that is refractory to treatment (mean survival after diagnosis approximately 3-5 years, or median of 28 months). An official statement from the respiratory societies (ATS/ERS/JRS/ALAT) regarding the diagnosis and management of IPF was published in 2011.


Definition / diagnosis

According to the consensus conference, the group of NSIP is provisional. Originally conceived as an umbrella term for all otherwise non-classifiable forms of IIP, NSIP has been an entity in its own right since the last consensus conference and is based on the histopathological demonstration of an NSIP pattern, which shows a wide spectrum ranging from predominance of a chronic interstitial inflammation (cellular NSIP) to predominance of interstitial fibrosis (fibrotic NSIP). In contradistinction to the UIP pattern, the changes all appear to have the same age, with a predominantly homogeneous interstitial fibrosis of variable density. Intra-alveolar fibrotic processes are found in about one third of cases; fibrosis nests, as seen in UIP, are completely absent. Patients with a predominantly fibrosing reaction have a much worse prognosis compared with patients with a predominant inflammatory reaction. An additional complication is that the NSIP pattern is not specific for (idiopathic) NSIP but can also be seen in other syndromes, e.g. in collagen diseases, drug-induced pulmonary fibrosis and EAA. Thus, in pure clinical terms, it is much more difficult to classify than, for example, IPF and is based on the progression, cell findings on BAL and the HRCT.

Definition / diagnosis

The currently valid term COP (cryptogenic organising pneumonitis) describes, like the term BOOP (bronchiolitis obliterans organizing pneumonia) still current in German-speaking countries, one and the same clinical syndrome which is characterised histologically by an organising pneumonia with intraluminal organising fibrosis in the alveolar ducts and alveolar spaces. There is also a variable degree of bronchiolar intra-luminal polyps of granulation tissue (bronchiolitis obliterans) as well as an interstitial inflammatory reaction. The lesions show a patchy distribution with an apparently similar temporal development pattern. These histopathological changes may be seen in several pulmonary or extrapulmonary processes and may even be idiopathic. Among the diseases in which this histopathological pattern occurs are organising bacterial and non-bacterial infections, organising aspiration pneumonia, collagen disease and vasculitis, EAA, eosinophilic lung diseases, post–bone marrow transplantation, drug effects, organisation after the inhalation of toxic substances and chronic inflammatory bowel diseases.


The term RB-ILD covers a form of IIP which is also termed “condensation or smoker’s pneumonia” in German. Here, the cause is generally excessive smoking, with the development of bronchiolitis (respiratory bronchiolitis, RB). In pure RB, patients only have collapse of the small airways. In some patients the disease can take on more severe forms, however, in which case there are numerous pigmented macrophages intraluminally and mild to moderate clinical symptoms (dyspnoea, hypoxaemia). We then talk of RB-ILD. DIP was originally interpreted by Liebow as an expression of desquamation of the alveolar epithelium and thus it is also termed desquamative interstitial pneumonia. We now know that the accumulation of cells in the distal airways and alveoli in this form is of macrophages, as in RB-ILD. Histologically, the picture of DIP is similar to RB-ILD, but the distribution pattern is much more homogeneous and does not even have the bronchiolocentric distribution. There is also mild peribronchial fibrosis and extensive hyperplasia of the alveolar type II cells. The bronchiolocentric lesions are usually combined with centrilobular emphysema. DIP thus very likely represents one spectrum and RB-ILD another spectrum of a common disease which only differs in the degree to which the different compartments are accentuated (like bronchiolitis obliterans and organising pneumonia).

Acute interstitial pneumonia, first described by Hamman and Rich, is a rapidly deteriorating interstitial lung disease which even today still has a fatal course in at least 50%. Histologically, these patients are found to have the pattern of diffuse alveolar damage (DAD), characterised by hyaline membranes, alveolar oedema and a marked interstitial and alveolar inflammatory reaction. As a rule, the whole lung is uniformly affected. The changes cannot be differentiated from those found in the acute respiratory distress syndrome (ARDS). In the organisation phase, there is abundant type II cell hyperplasia and loose, fibrotic thickening of the alveolar septa. The disease is thought to be preceded clinically by a viral episode with myalgia, arthralgia, fever and malaise. The respiratory insufficiency develops relatively quickly. On initial contact, the picture of bilateral alveolar consolidation is often already present. Intubation with ventilation is more the rule and for many patients the ARDS criteria also apply. Recovery is possible but may also progress towards the terminal picture of honeycomb lung.

LIP was also described as early as 1969 by Liebow. For many years, the significance was low in view of the inability to differentiate it from pulmonary lymphomas (mucosa-associated lymphoid tissue [MALT] lymphomas). It was only with the newer molecular biology and immunohistochemical methods that it was possible to reliably differentiate malignant from reactive changes. Pure idiopathic LIP is certainly a very rare disease, occasionally it occurs in conjunction with underlying systemic diseases such as rheumatoid arthritis, Sjögren’s syndrome, pernicious anaemia, chronic active hepatitis, SLE, primary biliary cirrhosis, myasthenia gravis, severe immune deficiency syndromes (AIDS) and others. The disease more frequently affects women in the fifth decade of life and has a slow progressive course with dry cough and exertional dyspnoea. There is rarely a marked fibrosing reaction, but instead extensive, diffusely distributed infiltration of the alveolar septa with lymphocytes, plasma cells and histiocytes, often also with the hyperplasia of MALT. However, a distribution along the lymphatics (bronchovascular bundle, pleura, interlobular septa) should suggest lymphoma. The pneumocytes are hyperplastic and intra-alveolar organisation tissue is also occasionally present. The HRCT is marked by a ground glass appearance and reticular markings, and occasionally perivascular cysts or honeycombing.

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