Introduction
Research strategies and literature analysis
Epidemiology
Pathogenesis
Etiologic agents
Environmental source class | Representative pathogens |
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Bacteria and mycobacteria | Thermophilic actinomycetes, Mycobacterium avium complex |
Fungi | Aspergillus spp., Alternaria spp., Penicillium spp., Trichosporon spp. |
Animal-derived proteins | Bird allergens, animal fur, cow’s milk |
Plant proteins | Grain proteins, tea plants, coffee-bean dust |
Chemicals | Plastics (e.g. isocyanates, anhydrides), detergents, pesticides (e.g. pyrethrum), e-cigarette liquids |
The host immune response
Clinical presentation and disease classifications
Criteria (> 2 are needed for the definition of acute exacerbation) | • Increase in respiratory rate > 20% from baseline • Onset or increase of dyspnea • Newly developing or increased abnormalities on chest imaging • Onset/increase of oxygen demand to achieve baseline saturation (at rest and/or during exercise) • Need for a supplementary level of ventilatory support (in addition to oxygen) • Decrease in vital capacity at spirometry in children able to perform the tests (> 10%) from baseline • Reduced exercise tolerance in children able to perform the tests (including desaturation) |
Diagnosis
Suggestive characteristics for HP: 1. Known exposure history to trigger antigen a. positive aerobiological and microbiological environmental investigations b. Sieric specific IgG levels [precipitins, ELISA, ImmunoCAP] 2. Compatible HRCT patternsa 3. Lymphocytosis at BAL (aspecific, not always necessary) 4. Positive inhalation challenge (only in selected patients) • Environmental restatement • Provocation test to the antigen | CONFIDENT HP without biopsy: - Criteria 1 + 2 + 3: Histopathologic confirmation not necessary - Criteria 1 + 2: BAL not necessary in case of clear exposition, typical HRCT, and response after antigen avoidance PROBABLE HPb - Criteria 1 (a or b) + 3; HRCT consistent with other lung diseases - Criteria 2 + 3; no environmental exposure or serologic evidence POSSIBLE HPb - Criteria 1 (a or b); HRCT consistent with other lung diseases; BAL not performed or without lymphocytosis - Criteria 1 (a or b) + 2; BAL without lymphocytosis |
Anamnesis
Lung imaging
Laboratory studies
Pulmonary function tests
Antigen identification
Bronchoscopy, bronchoalveolar lavage (BAL) and lung biopsy
Diagnostic algorithm
Differential diagnosis
Sweat test | Cystic fibrosis |
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Cardiological evaluation (ECG, echocardiogram) | Congenital heart disease |
Cultures or tests for infectious aetiology | Lung infections |
Oesophagal transit X-ray, pH-impedancemetry | Recurrent aspiration (GERD, dysphagia, anatomical abnormalities) |
Immunity studies IgA-M-G; recall Ag; HIV Lymphocyte subpopulations; Complement | Immunodeficiencies |
Studies for connective tissue diseases Anti-nuclear antibodies (ANA) Angiotensin-converting enzyme (ACE) Anti-neutrophil cytoplasmic (ANCA) Anti-glomerular basement membrane (GBM) | Autoimmune diseases Sarcoidosis Vasculitis (e.g., Wegener syndrome, Churg-Strauss syndrome, microscopic polyangiitis) Anti-GBM syndrome (Goodpasture syndrome) |
Serum and urinary amino acids | Lysosomal storage diseases Protein intolerance with lysinuria |
Genetics for surfactant dysfunctional diseases | Deficit of surfactant production and metabolism |
Bronchoscopy, BAL and lung biopsy | Infections, aspiration, Langerhans cell histiocytosis, alveolar haemorrhage, pulmonary alveolar proteinosis |