Table 1 Rules for allocating a “final working diagnosis” to the disease categories and subcategories

1. A final working diagnosis is established based on the available information

The final working diagnosis is the diagnosis with the highest likelihood. Even if some diagnostic tests are missing or the information level is low, a final working diagnosis is defined and used for categorization. Clinical symptoms (cough, dyspnea, etc.) are only considered informative for categorization if typical for the diagnosis

-Sarcoidosis is diagnosed based on chronic dyspnea, interstitial fine nodules, granulomatous skin lesions in biopsy, and increased angiotensin converting enzyme levels.

-Respiratory distress in the mature neonate as DPLD is diagnosed after the exclusion of infectious, cardiac, metabolic, neurologic and localized pulmonary causes.

-Tachypnoe in infants with NEHI

2. DPLD or not? Are any aspects of the final working diagnosis related to DPLD?

(a) Yes: the case should be categorized in the DPLD system

-Child with juvenile myelomonocytic leukemia and dyspnea, cough and reversible airway obstruction. On CT scan no evidence for obliterative bronchiolitis and bronchiectasis.

(b) No: no categorization in the DPLD system

⇨Airway disease, no DPLD

-Same history with same findings, but on CT scan septal thickening and centrilobular nodules

⇨DPLD-in the immunocompromised host or transplanted (B3)

-Pneumonia in a patient with chronic granulomatous disease, no evidence of an interstitial lung disease

⇨systemic disease, no DPLD

3. Systemic or lung-only condition? Is the lung disease part of a systemic disease process or is it a lung-only condition?

a) Allocation of a lung disease as part of a systemic disease process is preferred over classifying as lung-only DPLD, if there is any evidence for the involvement of systemic structures

-Clinical, BAL or histological evidence for pulmonary hemorrhage without any evidence for systemic involvement, diagnosis of idiopathic pulmonary hemosiderosis

Reason: it is more likely that the systemic disease causes a lung problem, than that an independent rare lung disease emerges in addition to a DPLD related to a systemic disease.

⇨DPLD - related to lung vessels structural processes (B4)

Consequences:

-Pulmonary hemorrhage and a disease-causing mutation for Osler’s disease

⇨DPLD - related to systemic disease processes (B1)

(i) same histological pattern may be present in different categories

-Pulmonary hemorrhage and celiac disease

⇨DPLD - related to systemic disease processes (B1)

(ii) carefully re-evaluate for potential lung disease only

b) Allocation of a disease as a lung-only DPLD in the presence of hints for the involvement of systemic structures should only be done if convincing evidence supports a lung-only DPLD

-Acute lymphatic leukemia treated with chemotherapy and stem cell transplant, development of pulmonary pathology, histologically NSIP

⇨DPLD – related to systemic disease processes (B1): lung injury as a complication or therapy more likely than independent lung disease

-Same history, but detection of two disease causing ABCA3 mutations in the patient

⇨DPLD – related to alveolar surfactant region (A4): lung-only DPLD in addition to oncologic disease

4. Select a category and a subcategory which best accommodates the final working diagnosis

Prefer the category/subcategory with

(a) a better causal link/explanation for the lung disease: cause of pulmonary disease is for example ranked higher than the histological pattern alone, since the same histological result can be allocated to several categories. If the cause is not determinable, the most likely association of the histological pattern with a disease is selected.

-a patient with a drug-induced hypersensitivity reaction of the lung and the histological pattern of NSIP

⇨DPLD - in the presumed immune intact host, related to exposures (B2)

-A patient with NSIP and no further clinical information

⇨DPLD - related to the alveolar surfactant region (A4) is selected and awaits further molecular characterization, as NSIP can be associated with SFTPC, ABCA3, or TTF1/Nkx2.1 mutations

(b) the overall better proof, even if less specific

-BPD-cLDI is preferred over pulmonary hypoplasia as the latter can reliably only be assessed by radial counting of pathology specimens or experimentally by using novel imaging techniques not routinely available