Difference between revisions of "Medical lung diseases"

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*[[Acute infectious pneumonia]].
*[[Acute infectious pneumonia]].
*[[Chronic infectious pneumonia]].
*[[Chronic infectious pneumonia]].
*Others.
==Diffuse lung diseases==
{{Main|Diffuse lung diseases}}
These are also known as ''idiopathic interstitial pneumonias''.


==Asthma==
==Asthma==
Line 176: Line 171:
*Elastic trichrome - useful for delineation of obliterated bronchioles.
*Elastic trichrome - useful for delineation of obliterated bronchioles.


==Diffuse lung diseases==
{{Main|Diffuse lung diseases}}
These are also known as ''idiopathic interstitial pneumonias''.


==Fibrosis==
==Fibrosis==

Revision as of 06:34, 28 December 2011

The medical lung diseases are a huge topic. Most pathologists have little to do with 'em. They are the domain of respirology. An introduction to lung pathology is in the lung article, along with a general approach. Interstitial lung disease is dealt with in the diffuse lung diseases article.

Infectious pneumonia

Main article: Pneumonia

Includes:

Asthma

General

  • The bread and butter of respirology.
  • May be associated with atopy (allergies), medications (e.g. NSAIDs), occupational exposures.[1]

Pathogenesis

  • T-cell response TH2 dominant.

Sequence:[2]

  • Antigen TH2 lymphocyte -> IgE B-cell -> mast cell IgE Fc -> leukotrienes + other mediators -> bronchospasm, edema, leukocyte recruitment -> airway remodeling.

Gross

  • Lung over-inflation.
  • Mucous plugs.
  • Focal resorption atelectasis,[3] i.e. collapse.

Microscopic

Features:[4]

  • Edema.
  • Mucous (plugs).
  • +/-Smooth muscle hypertrophy.
  • +/-Inflammation - especially with eosinophils.
  • +/-Charcot-Leyden crystals (formed from eosinophil granules -- breakdown product).
    • Sharp edge, diamond shaped, intense pink.

Images:

Notes:

  • Leyden in Charcot-Leyden is also seen written as Leiden.
  • Pulmonary cytopathology: Curschmann's spirals - spiral-shaped mucous plugs.[5]

Emphysema

General

Pathologic classification

Based on morphology:[7]

  1. Centriacinar (centrilobular) - associated with heavy smoking.
  2. Panacinar (panlobular) - associated with alpha-1 antitrypsin deficiency.
  3. Distal (paraseptal) acinar - associated with spontaneous pneumothorax.
  4. Irregular - usu. insignificant.
  • Q. Why does smoking lead to centriacinar emphysema?
  • A. The bad stuff from smoking gets enters the acinus at the centre; ergo, this is the location of the most damage.

Gross

  • Holes (blebs, bullae), usually upper lung field predominant.
  • Lungs may overlap the heart.[8]

Notes:

  • Bleb = (small) vesicle.[9]
  • Bulla = large vesicle.[10]

Microscopic

Features:[8]

  • Large alveoli.
  • Thin septa (no interstitial thickening).

Image:

Chronic bronchitis

General

  • Often seen together with emphysema with which it is lumped together with in the term COPD.
  • It's a clinical diagnosis - criteria:[1]
    • Cough with sputum for thee months in at least two consecutive years.
    • No other cause identified.

Clinical:[1]

  • Blue bloater (carbon dioxide retainers)
  • Develop cor pulmonale.

Microscopic

Features:[1]

  • Mucous gland hypertrophy + mucinous secretions in airway.
  • Goblet cell metaplasia.
  • Bronchiolar inflammation and fibrosis.

Pulmonary edema

General

  • Seen in a number of conditions, e.g. congestive heart failure.

Microscopic

Features:[11]

  • Dilated capillaries.
  • Blood in airspace.
  • Plasma proteins in airspace - light pink acellular junk.
  • +/-Hemosiderin-laden macrophages (heart failure cells).

Organizing pneumonia

General

  • Multiple causes, e.g. transplant rejection, infection.

Clinical diagnoses:[12]

Note:

  • BOOP is used as a synonym for organizing pneumonia which has the long differential diagnosis above.[12]
    • Confusingly, it may be used to refer to the idiopathic form of organizing pneumonia, now generally known as cryptogenic organizing pneumonia (COP).
      • In other words, strictly speaking, BOOP is not the same as COP; idiopathic BOOP is COP.

Microscopic

Features:[13]

  • Distal airway disease -- airways plugged with organizing exudate ("Masson bodies").
    • "Organized exudate" = fluffy light-staining paucicellular regions with stellate cells (fibroblasts & immature connective tissue).

Images:

Constrictive bronchiolitis

  • AKA bronchiolitis obliterans, AKA obliterative broncholitis,[15] AKA bronchiolitis obliterans syndrome (BOS).[16]

General

  • Not the same as (idiopathic) bronchiolitis obliterans organizing pneumonia (BOOP) - in short:
    • BOOP: clogs the airway, has Masson bodies, treated with steroids - good prognosis.
    • Constrictive bronchiolitis: fibrosis around airways, crappy prognosis.
  • No good treatment.
  • Progressive.

Etiology/associations:[15]

  • Post-infectious.
    • Viral.
    • Mycoplasma.
  • Post-lung transplant.[17]
  • Post-hematopoietic stem cell transplantation
    • Associated with GVHD.[17]
  • Connective tissue disease, mostly rheumatoid arthritis.
  • Ulcerative colitis.
  • Drugs - penicillamine.
  • Toxins.
  • Idiopathic.

Microscopic

Features:[15]

  1. Bronchiolitis - mononuclear and neutrophilic.
    • May be minimal late in the disease.
  2. Fibrosis - submucosal and peribronchiolar.
    • Can be patchy.

Notes:

  • Bronchioles = noncartilagenous airways usu. < 2 mm in diameter.[15]

Images:

Stains

  • Elastic trichrome - useful for delineation of obliterated bronchioles.

Diffuse lung diseases

Main article: Diffuse lung diseases

These are also known as idiopathic interstitial pneumonias.

Fibrosis

Histomorphological classification

  1. Hyaline membranes - glassy pink material lining airways & alveoli.
  2. Microscopic honeycombing - "holes" in the lung.
  3. Bronchiolization - ciliated (respiratory) epithelium in distal airway.
  4. Uniform alveolar septal thickening - septae look similar at low power.
  5. Peripheral lobular fibrosis - septae thickening peripheral, HRCT shows: irregular peripheral reticular opacities.[18]
    • Reticular = net-like.[19]
  6. Siderophages in alveoli - macrophages with hemosiderin the alveoli.
  7. Fibrinous pleuritis - peripheral only (based on imaging).
  8. Granulomata, non-necrotizing.
  9. Abundance of vacuolated cells.
  10. Chronic inflammation.
  11. Bronchiolocentric scarring - fibrosis concentrated around airway/assoc. with airway.

Radiologic/gross pathologic DDx by location

Causes of lower lung fibrosis BAD RASH:[20]

Note:

Causes of upper lung fibrosis FASSTEN:[22]

Prognosis

  • The pattern and severity of fibrosis seems to be the most important factors prognostically - more important than the underlying cause (ILD, CVD, drug reaction etc.).[23][24]

Patterns of fibrosis:

  • "Linear" - follows alveolar walls, no architectural distortion.
  • UIP-like (honeycombing).

Disease with fibrosis

There are many of 'em.

Lymphocytic lesions of the lung

Diagnosis Key histologic feature Radiology Other diagnostic
Lymphocytic interstitial pneumonia interstitial lymphoid cells, usu. no nodules interstitial pattern
Follicular bronchiolitis/bronchitis lymphoid cell around bronchioles / bronchus, normal parenchyma interstitial pattern
Nodular lymphoid hyperplasia abundant lymphoid cells in nodules nodules /interstitial pattern stains to exclude lymphoma; germinal centres do not exclude lymphoma
Lymphoma (BALToma) abundant lymphoid cells usu. in nodules nodules / interstitial pattern may require stains to prove, germinal centres may be present

Lymphocytic interstitial pneumonia

Main article: Lymphocytic interstitial pneumonia

Follicular bronchitis/bronchiolitis

General

Gross/radiology

  • No distinct nodule or mass.
  • Classically: increased reticular marking, i.e. interstitial pattern.

Images: Intersitial pattern - radiographs (ucsf.edu).

Microscopic

Features:[28]

  • Peribronchiolar/peribronchial lymphoid nodules with:
    • Reactive germinal centres.
      • Lack of these should raise suspicion for lymphoma.
    • Plasma cells.
  • +/-Lymphoid nodules in the interlobular septa.

Notes:

  • Lung parenchyma distant from nodule = normal; no lymphocytic infiltrate.

DDx:

Nodular lymphoid hyperplasia

General

  • AKA pseudolymphoma - a term some dislike.[28]
  • Definition - reactive lymphoid cells.

Gross/radiology

  • Has nodules radiographically.

Microscopic

Features:[28]

  • Reactive lymphoid nodules.

Notes:[29]

  • Presence of germinal centres do not exclude lymphoma - may still be a BALToma.
    • BALT = bronchial/bronchus associated lymphoid tissue.

DDx:

Smoking associated disease

Main article: Smoking
  • RB = respiratory bronchiolitis.
  • RBILD = respiratory bronchiolitis interstitial lung disease.
  • DIP = desquamative interstitial pneumonia.
  • Eosinophilic granuloma (of lung) - AKA pulmonary langerhans cell histiocytosis.

All of the above are assoc. with smoking. RBILD & DIP are considered by many to be on a continuum, i.e. RBILD is early DIP.

Respiratory bronchiolitis

  • Diagnosis is based on clinical criteria.

Microscopic

Features:

  • Inflammation.
  • No interstitial lung disease, i.e. no fibrosis.

Respiratory bronchiolitis interstitial lung disease

Main article: Respiratory bronchiolitis interstitial lung disease

Desquamative interstitial pneumonia

Main article: Desquamative interstitial pneumonia

Pulmonary Langerhans cell histiocytosis

  • AKA eosinophilic granuloma of the lung.

General

Subtypes:[30]

  • Cellular form.
  • Fibrotic form.

One form usually predominates.

Radiology

  • Upper lung zones.

Microscopic

Features:[31]

  • Cellular peribronchiolar nodules with:
    • Langerhans cells - key feature:
      • Pale staining nucleus (H&E) with nuclear infolding - "crumpled tissue paper" appearance.
    • +/-Smoker's macrophages (brown pigmented airspace macrophages).
    • +/-Eosinophilia (may be rare) - significantly narrow DDx.
    • Chronic inflammatory cells (lymphocytes). (???)

IHC

  • Langerhans cells: S100+ and CD1a+.[31]

Granulomatous lung disease

See: Granulomas for an introduction to the general topic.

Most common:

  • Infectious - mycobacterial and fungal.[32]

Noninfectious causes:[32]

  • Aspiration pneumonia.
  • Hypersensitivity pneumonitis.
  • Hot tub lung.
  • Talc granulomatosis.
  • Sarcoidosis.
  • Wegener granulomatosis.

Sarcoidosis

Main article: Sarcoidosis

General

  • Diagnosis of exclusion - infection must be excluded.
  • Radiologic differential diagnosis includes carcinomatosis.[33]

Microscopic

Features:

  • Granulomata, well-formed, non-necrotizing.
    • Negative for microorganisms with special stains (PAS-D, GMS, AFB).
    • Granulomata - interstitial location.

Image(s):

Pulmonary talcosis

General

  • Associated with herion use.[34]
  • X-ray findings similar to asbestosis.

Microscopic

Features:

  • Granulomas with foreign material.
    • Foreign material often polarizes.

Images:

Miscellaneous diseases

Pneumocytoma

General

  • Previously known as sclerosing hemangioma.
  • AKA sclerosing hemangioma.
  • Derived from type 2 pneumocyte.[35]
  • Progesterone-receptor positive stromal cells.[36]

Epidemiology

  • Female in 40s.[37]
  • Considered benign; excision is curative.
    • Rare case reports of metastases.

Gross

  • Peripheral, solitary.
  • Well-circumscribed.

Microscopic

Features:[37]

  • Mixed cell population.
  • Variable architecture:
    • Papillary.
    • Sclerotic.
    • Solid.
    • Hemorrhagic.
  • +/-Granulomas.

DDx:[38]

IHC

Features:[35]

  • TTF-1 +ve.
  • HNF-3 alpha +ve.
  • HNF-3 beta +ve.

Lymphangioleiomyomatosis

  • Abbreviated LAM.
  • AKA lymphangiomyomatosis.

General

  • Clinical: dyspnea, recurrent pneumothorax.
  • May be an indication for lung transplantation.
  • Non-neoplastic muscle proliferation vs. tumour that can metastasize.[39]

Notes:

Epidemiology

Radiology

  • Bullae/thin walled cysts - distributed in all lung fields.
  • Lymphadenopathy.

Radiologic DDx (of cysts):

  • Eosinophilic granuloma (assoc. with smoking).
  • Interstitial pulmonary fibrosis (UIP).
  • Emphysema.

Microscopic

Features:[42]

  • Spindle cells with small nuclei + larger epithelioid cells with clear cytoplasm and round nuclei.
  • Cyst formation.
  • Thick arterial walls.

Images:

IHC

  • HMB-45 +ve.
  • ER +ve.
  • PR +ve.
  • SMA +ve.

Pulmonary alveolar proteinosis

  • Abbreviated PAP.

General

  • Associated with smoking - particularily in men.[43]

Pathophysiology:

  • GM-CSF (granulocyte-macrophage colony stimulating factor) signaling in macrophages/lack of GM-CSF.
    • GM-CSF is required by alveolar macrophages to clear surfactant.

Classification:[43]

  1. Congenital:
      • Abnormal surfactant.
      • GM-CSF receptor defect.
  2. Secondary:
    • Infections.
    • Haematologic malignancy.
  3. Acquired:
    • Dusts - interfere with macrophage function.

Clinical:

  • Dyspnea & cough - gradual onset.

Radiology

Microscopic

Features:

  • Crap in the alveoli:
  • "Dense bodies" - dead macrophages ("Chatter" in the alveoli).
    • Edema - has pink stuff in the alveoli like PAP but no dense bodies.

DDx - may mimic:[44]

  • Edema.
  • Pneumocystis - exudates foamy & vacuolated.
  • Pulmonary hemorrhage (acute). (???)

Images:

Images of DDx:

Drug reactions

  • Effects are often non-specific.

Website: http://www.pneumotox.com

Pulmonary hypertension

Main article: Pulmonary hypertension

General classification:

  • Primary, i.e. primary pulmonary hypertension, or
  • Secondary, e.g. due to congenital heart disease (like ventricular septal defect), interstitial pulmonary fibrosis.

Non-secondary pulmonary hypertension

Main article: Pulmonary hypertension

Causes:[46]

Severity

Eosinophilic pneumonia

Specific entities:[47]

  • Churg-Strauss syndrome.
  • Acute eosinophilic pneumonia.
  • Chronic eosinophilic pneumonia.
  • Eosinophilic granuloma (pulmonary histiocytosis X, Langerhans cell granulomatosis).

Entities which may have eosinophilia as prominent feature:

  • AIDS.
  • Lymphoma.
  • Collagen vascular disease.

Churg-Strauss syndrome

Main article: Churg-Strauss syndrome

Microscopic

Features:

Lung transplant pathology

Main article: Lung transplant pathology

This subspecialty is dealt with in its own article.

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 370. ISBN 978-1416054542.
  2. ↑ Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 370-2. ISBN 978-1416054542.
  3. ↑ Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 363. ISBN 978-1416054542.
  4. ↑ Klatt, Edward C. (2006). Robbins and Cotran Atlas of Pathology (1st ed.). Saunders. pp. 108. ISBN 978-1416002741.
  5. ↑ Cenci M, Giovagnoli MR, Alderisio M, Vecchione A (November 1998). "Curschmann's spirals in sputum of subjects exposed daily to urban environmental pollution". Diagn. Cytopathol. 19 (5): 349–51. PMID 9812228.
  6. ↑ Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 368. ISBN 978-1416054542.
  7. ↑ Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 368. ISBN 978-1416054542.
  8. ↑ 8.0 8.1 Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 369. ISBN 978-1416054542.
  9. ↑ URL: http://dictionary.reference.com/browse/bleb. Accessed on: 3 August 2011.
  10. ↑ URL: http://dictionary.reference.com/browse/bulla. Accessed on: 3 August 2011.
  11. ↑ Klatt, Edward C. (2006). Robbins and Cotran Atlas of Pathology (1st ed.). Saunders. pp. 102. ISBN 978-1416002741.
  12. ↑ 12.0 12.1 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 91. ISBN 978-0781765275.
  13. ↑ Klatt, Edward C. (2006). Robbins and Cotran Atlas of Pathology (1st ed.). Saunders. pp. 110. ISBN 978-1416002741.
  14. ↑ URL: http://150.59.224.157/pathology/index.php?first_category_id=2&second_category_id=20. Accessed on: 4 August 2011.
  15. ↑ 15.0 15.1 15.2 15.3 Visscher, DW.; Myers, JL. (2006). "Bronchiolitis: the pathologist's perspective.". Proc Am Thorac Soc 3 (1): 41-7. doi:10.1513/pats.200512-124JH. PMID 16493150. http://pats.atsjournals.org/cgi/content/full/3/1/41.
  16. ↑ Sato, M.; Keshavjee, S. (2008). "Bronchiolitis obliterans syndrome: alloimmune-dependent and -independent injury with aberrant tissue remodeling.". Semin Thorac Cardiovasc Surg 20 (2): 173-82. doi:10.1053/j.semtcvs.2008.05.002. PMID 18707652.
  17. ↑ 17.0 17.1 Chien, JW.; Duncan, S.; Williams, KM.; Pavletic, SZ. (Jan 2010). "Bronchiolitis obliterans syndrome after allogeneic hematopoietic stem cell transplantation-an increasingly recognized manifestation of chronic graft-versus-host disease.". Biol Blood Marrow Transplant 16 (1 Suppl): S106-14. doi:10.1016/j.bbmt.2009.11.002. PMID 19896545.
  18. ↑ http://www.rsna.org/Publications/rsnanews/may06/jrnl_may06.cfm
  19. ↑ http://dictionary.reference.com/browse/reticular
  20. ↑ TN05 R13.
  21. ↑ Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 90. ISBN 978-0781765275.
  22. ↑ TN05 R13.
  23. ↑ Bjoraker JA, Ryu JH, Edwin MK, et al. (January 1998). "Prognostic significance of histopathologic subsets in idiopathic pulmonary fibrosis". Am. J. Respir. Crit. Care Med. 157 (1): 199-203. PMID 9445300. http://ajrccm.atsjournals.org/cgi/content/full/157/1/199.
  24. ↑ AC UBC S.425.
  25. ↑ Nicholson AG (August 2001). "Lymphocytic interstitial pneumonia and other lymphoproliferative disorders in the lung". Semin Respir Crit Care Med 22 (4): 409–22. doi:10.1055/s-2001-17384. PMID 16088689.
  26. ↑ Aerni MR, Vassallo R, Myers JL, Lindell RM, Ryu JH (February 2008). "Follicular bronchiolitis in surgical lung biopsies: clinical implications in 12 patients". Respir Med 102 (2): 307–12. doi:10.1016/j.rmed.2007.07.032. PMID 17997299.
  27. ↑ Kinane BT, Mansell AL, Zwerdling RG, Lapey A, Shannon DC (October 1993). "Follicular bronchitis in the pediatric population". Chest 104 (4): 1183–6. PMID 8404188.
  28. ↑ 28.0 28.1 28.2 AFIP atlas of nontumour pathology. 2002. Vo. 2. P.277. ISBN 1-881041-79-4.
  29. ↑ AFIP atlas of nontumour pathology. 2002. Vo. 2. P.281. ISBN 1-881041-79-4.
  30. ↑ 30.0 30.1 Leslie, Kevin O.; Wick, Mark R. (2004). Practical Pulmonary Pathology: A Diagnostic Approach (1st ed.). Churchill Livingstone. pp. 234. ISBN 978-0443066313.
  31. ↑ 31.0 31.1 Leslie, Kevin O.; Wick, Mark R. (2004). Practical Pulmonary Pathology: A Diagnostic Approach (1st ed.). Churchill Livingstone. pp. 237. ISBN 978-0443066313.
  32. ↑ 32.0 32.1 Mukhopadhyay S, Gal AA (May 2010). "Granulomatous lung disease: an approach to the differential diagnosis". Arch. Pathol. Lab. Med. 134 (5): 667–90. PMID 20441499.
  33. ↑ URL: http://www.radiologyassistant.nl/en/46b480a6e4bdc. Accessed on: 23 May 2010.
  34. ↑ Davis, LL. (Dec 1983). "Pulmonary "mainline" granulomatosis: talcosis secondary to intravenous heroin abuse with characteristic x-ray findings of asbestosis.". J Natl Med Assoc 75 (12): 1225–8. PMC 2561715. PMID 6655726. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2561715/.
  35. ↑ 35.0 35.1 Yamazaki, K. (Jul 2004). "Type-II pneumocyte differentiation in pulmonary sclerosing hemangioma: ultrastructural differentiation and immunohistochemical distribution of lineage-specific transcription factors (TTF-1, HNF-3 alpha, and HNF-3 beta) and surfactant proteins.". Virchows Arch 445 (1): 45-53. doi:10.1007/s00428-004-1023-3. PMID 15138814.
  36. ↑ Einsfelder, BM.; Müller, KM. (Sep 2005). "["Pneumocytoma" or "sclerosing hemangioma": histogenetic aspects of a rare tumor of the lung]". Pathologe 26 (5): 367-77. doi:10.1007/s00292-005-0751-8. PMID 15731902.
  37. ↑ 37.0 37.1 Keylock, JB.; Galvin, JR.; Franks, TJ. (May 2009). "Sclerosing hemangioma of the lung.". Arch Pathol Lab Med 133 (5): 820-5. PMID 19415961.
  38. ↑ URL: http://www.med.muni.cz/biomedjournal/pdf/2004/01/37_42.pdf. Accessed on: 17 June 2010.
  39. ↑ Taveira-DaSilva, AM.; Pacheco-Rodriguez, G.; Moss, J. (Mar 2010). "The natural history of lymphangioleiomyomatosis: markers of severity, rate of progression and prognosis.". Lymphat Res Biol 8 (1): 9-19. doi:10.1089/lrb.2009.0024. PMID 20235883.
  40. ↑ 40.0 40.1 http://emedicine.medscape.com/article/299545-overview
  41. ↑ Schiavina, M.; Di Scioscio, V.; Contini, P.; Cavazza, A.; Fabiani, A.; Barberis, M.; Bini, A.; Altimari, A. et al. (Jul 2007). "Pulmonary lymphangioleiomyomatosis in a karyotypically normal man without tuberous sclerosis complex.". Am J Respir Crit Care Med 176 (1): 96-8. doi:10.1164/rccm.200610-1408CR. PMID 17431222.
  42. ↑ http://emedicine.medscape.com/article/299545-diagnosis
  43. ↑ 43.0 43.1 Trapnell BC, Whitsett JA, Nakata K (December 2003). "Pulmonary alveolar proteinosis". N. Engl. J. Med. 349 (26): 2527-39. doi:10.1056/NEJMra023226. PMID 14695413. http://content.nejm.org/cgi/content/extract/349/26/2527.
  44. ↑ Leslie, Kevin O.; Wick, Mark R. (2004). Practical Pulmonary Pathology: A Diagnostic Approach (1st ed.). Churchill Livingstone. pp. 248. ISBN 978-0443066313.
  45. ↑ Leslie KO (May 2009). "My approach to interstitial lung disease using clinical, radiological and histopathological patterns". J. Clin. Pathol. 62 (5): 387–401. doi:10.1136/jcp.2008.059782. PMC 2668105. PMID 19398592. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668105/.
  46. ↑ Bush A (December 2000). "Pulmonary hypertensive diseases". Paediatr Respir Rev 1 (4): 361-7. doi:10.1053/prrv.2000.0077. PMID 16263465.
  47. ↑ http://emedicine.medscape.com/article/301070-overview

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