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Acute Interstitial Pneumonia
Introduction
Acute interstitial pneumonia (AIP - also known as Hamman-Rich syndrome) is an acute, rapidly progressive idiopathic pulmonary disease that often leads to fulminant respiratory failure and acute respiratory distress syndrome (ARDS).[1] It can be distinguished clinically from other types of interstitial pneumonia by the rapid onset of respiratory failure in a patient without preexisting lung disease.[2] Louis Hamman and Arnold Rich first described it in 1935 as a fulminating diffuse interstitial fibrosis of the lungs.[3] In 1986, Katzenstein introduced the term AIP differentiating it from the group of chronic interstitial pneumonia.[4][5] The American Thoracic Society (ATS) and European Respiratory Society (ERS) classify AIP under major idiopathic interstitial pneumonia, compared to other rare or unclassified idiopathic interstitial pneumonia.[1]
Etiology
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Etiology
Acute interstitial pneumonia (AIP) has no known etiology.
Epidemiology
The mean age of patients with AIP is around 55. There is no sex predilection.[4][5][6][7][8][9]
Pathophysiology
Acute interstitial pneumonia (AIP) is thought to be triggered by an unknown insult to the alveolar epithelium leading to activation of the inflammatory cascade, followed by fibroblastic activity in the late stage.[6]
Histopathology
Acute interstitial pneumonia (AIP) has the histopathological pattern of diffuse alveolar damage (DAD) that is indistinguishable from the histologic pattern found in ARDS.[1][4][7] The histologic discerption depends on the timing of the biopsy. The early phase (within a week of the initial tissue injury) is exudative, characterized by edema in the interstitium and alveolus. After that, a late phase, which is also called the organizing phase, shows fibroblastic proliferation and type 2 cell hyperplasia.[2][4][7]
History and Physical
Symptoms usually start as viral-like prodrome followed with shortness of breath with cough, and fever, progress rapidly to acute respiratory distress. The physical exam is nonspecific with hypoxia, tachypnea, and bilateral diffuse crackles. Many of those patients are severely hypoxemic and require mechanical ventilation.[5][6][7][9]
A detailed history with a comprehensive medical examination is essential to investigate for other causes of acute DAD, as noted below, under differential diagnosis.
Evaluation
Patients with Acute Interstitial Pneumonia are at risk of rapid respiratory decompensation. Vital signs should be monitored closely. Arterial blood gases can identify the severity of hypoxemia and the need for mechanical ventilation.
Chest X-ray usually shows a pattern that is similar to ARDS, which is a bilateral air-space diffuse opacities. Therefore, ruling out cardiac causes of pulmonary edema is essential. Echocardiography is needed to rule out underlying cardiomyopathy or valve dysfunction. High-Resolution Computed Tomography (HRCT) is usually abnormal in the first 12 hours. It shows ground-glass opacities and air space consolidation that can be diffuse or patchy. HRCT findings correlate with the different phases of DAD.[8][10][11][12] CT findings can also show traction bronchiectasis, indicating progression from the exudative phase to the proliferative fibrotic phase.[11]
Laboratory workup should include screening for autoimmune and connective tissue diseases that might be associated with lung disease, starting from rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) to dermatomyositis and Sjogren syndrome.[13]
Microbiologic workup should include blood and sputum culture. Influenza screening is important, as well as serology for atypical organisms and fungus. Legionella is an atypical organism that can be detected on urine antigen test. Bronchoscopy with bronchoalveolar lavage (BAL) is needed to exclude diffuse alveolar hemorrhage (DAH), eosinophilia, or malignant infiltrates. In acute interstitial pneumonia, BAL results are usually non-specific with neutrophilia and scattered atypical type II pneumocytes.[14] Bronchoscopy also helps in obtaining respiratory samples for culture in the absence of sputum production. The sample should be sent for cell count and cytology, cultures, and Pneumocystis jirovecii immunofluorescence.
If the previous workup fails to achieve an alternative diagnosis, lung biopsy might be indicated. Lung biopsy might also reveal different etiologies like caseating granulomas (tuberculosis), non-caseating granulomas (sarcoidosis), necrosis (vasculitis), abscesses, or viral inclusion.
Acute interstitial pneumonia is an idiopathic disease. After excluding other causes of ARDS, pathologic confirmation of idiopathic DAD is necessary to establish the diagnosis.
Treatment / Management
There is no proven treatment in AIP.[1] Management is largely based on supportive care. Adequate oxygenation often cannot be achieved without mechanical ventilation.[9][15] As in ARDS, arterial blood gases can identify the severity of respiratory distress based on the Berlin Criteria (PaO2/FiO2).[16][17] Ventilator management mainly focuses on low tidal volume ventilation and other advanced ventilator modalities such as those used in ARDS.[16][17] (A1)
Broad-spectrum antibiotics are recommended initially until infectious etiology is excluded.
Despite that steroid therapy is usually started empirically, it has no clear benefit in AIP. In a case series of 29 patients with AIP, 12 patients survived. Survival was 45% compared to 33% in patients who did vs. did not receive steroids, respectively.[7] Meanwhile, the mortality was 100% in a different case series of 9 patients who all received IV methylprednisolone 2 mg/kg 4 times a day.[15] (B2)
Extracorporeal membrane oxygenation (ECMO) and lung transplantation should be considered for appropriate candidates after failing conventional therapy.[9][15][18](B2)
Differential Diagnosis
Differential diagnosis of acute interstitial pneumonia includes:
- Other causes of interstitial pneumonia such as cryptogenic organizing pneumonia, acute eosinophilic pneumonia, and hypersensitivity pneumonitis
- Acute exacerbation of underlying interstitial lung disease or pulmonary exacerbation of a connective tissue disease
- Acute heart failure
- Infections
- Diffuse alveolar hemorrhage
- Drug-induced lung injury
- Radiation-induced lung injury
Prognosis
The mortality rate is greater than 50%, either in the initial presentation or within six months after onset. [1][4][5][7][9][15] Also, in survivors, recurrence, and development of chronic interstitial lung disease were reported.[9]
Deterrence and Patient Education
- Acute interstitial pneumonia is a disease with unclear causes, so it is hard to prevent or predict its onset
- Initial Symptoms are non-specific to the disease as any other respiratory disease.
- Patients should seek medical advice earlier before respiratory deterioration.
- There is no specific test for acute interstitial pneumonia, and the only way to confirm it is a lung biopsy.
- There is no specific medication to treat acute interstitial pneumonia. Management is generally supportive.
Pearls and Other Issues
- AIP usually has a similar presentation to ARDS.
- AIP is only diagnosed after excluding other etiologies of diffuse alveolar hemorrhage.
- There is no specific treatment for AIP. Management is mostly supportive.
- Empiric broad-spectrum antibiotics should be started empirically until infection is excluded.
- A lung-protective strategy should be implemented.
- Treatment with steroids has no clear benefit in AIP.
- Mortality is high, and lung transplant should be considered for appropriate candidates.
Enhancing Healthcare Team Outcomes
Acute interstitial pneumonia is an uncommon disease that presents acutely and progresses rapidly with a high rate of mortality. Diagnosis is complex and requires an interprofessional team, including pulmonology, radiology, and pathology. Proper communication and coordination between members of the healthcare team can fasten the diagnosis process, and therefore initiate the management earlier. The primary team also should be aware of the possible complication that may arise during the acute illness. Generally, the medical community still needs a better understanding of the initial triggers and progression of the disease to improve the outcome.
References
Travis WD, Costabel U, Hansell DM, King TE Jr, Lynch DA, Nicholson AG, Ryerson CJ, Ryu JH, Selman M, Wells AU, Behr J, Bouros D, Brown KK, Colby TV, Collard HR, Cordeiro CR, Cottin V, Crestani B, Drent M, Dudden RF, Egan J, Flaherty K, Hogaboam C, Inoue Y, Johkoh T, Kim DS, Kitaichi M, Loyd J, Martinez FJ, Myers J, Protzko S, Raghu G, Richeldi L, Sverzellati N, Swigris J, Valeyre D, ATS/ERS Committee on Idiopathic Interstitial Pneumonias. An official American Thoracic Society/European Respiratory Society statement: Update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. American journal of respiratory and critical care medicine. 2013 Sep 15:188(6):733-48. doi: 10.1164/rccm.201308-1483ST. Epub [PubMed PMID: 24032382]
Bouros D, Nicholson AC, Polychronopoulos V, du Bois RM. Acute interstitial pneumonia. The European respiratory journal. 2000 Feb:15(2):412-8 [PubMed PMID: 10706513]
Hamman L, Rich AR. Fulminating Diffuse Interstitial Fibrosis of the Lungs. Transactions of the American Clinical and Climatological Association. 1935:51():154-63 [PubMed PMID: 21407504]
Katzenstein AL,Myers JL,Mazur MT, Acute interstitial pneumonia. A clinicopathologic, ultrastructural, and cell kinetic study. The American journal of surgical pathology. 1986 Apr; [PubMed PMID: 3706612]
Katzenstein AL, Myers JL. Idiopathic pulmonary fibrosis: clinical relevance of pathologic classification. American journal of respiratory and critical care medicine. 1998 Apr:157(4 Pt 1):1301-15 [PubMed PMID: 9563754]
Vourlekis JS. Acute interstitial pneumonia. Clinics in chest medicine. 2004 Dec:25(4):739-47, vii [PubMed PMID: 15564019]
Olson J, Colby TV, Elliott CG. Hamman-Rich syndrome revisited. Mayo Clinic proceedings. 1990 Dec:65(12):1538-48 [PubMed PMID: 2255216]
Level 2 (mid-level) evidencePrimack SL, Hartman TE, Ikezoe J, Akira M, Sakatani M, Müller NL. Acute interstitial pneumonia: radiographic and CT findings in nine patients. Radiology. 1993 Sep:188(3):817-20 [PubMed PMID: 8351354]
Vourlekis JS, Brown KK, Cool CD, Young DA, Cherniack RM, King TE, Schwarz MI. Acute interstitial pneumonitis. Case series and review of the literature. Medicine. 2000 Nov:79(6):369-78 [PubMed PMID: 11144035]
Level 3 (low-level) evidenceIchikado K, Johkoh T, Ikezoe J, Takeuchi N, Kohno N, Arisawa J, Nakamura H, Nagareda T, Itoh H, Ando M. Acute interstitial pneumonia: high-resolution CT findings correlated with pathology. AJR. American journal of roentgenology. 1997 Feb:168(2):333-8 [PubMed PMID: 9016201]
Level 2 (mid-level) evidenceIchikado K. High-resolution computed tomography findings of acute respiratory distress syndrome, acute interstitial pneumonia, and acute exacerbation of idiopathic pulmonary fibrosis. Seminars in ultrasound, CT, and MR. 2014 Feb:35(1):39-46. doi: 10.1053/j.sult.2013.10.007. Epub 2013 Oct 22 [PubMed PMID: 24480142]
Johkoh T, Müller NL, Taniguchi H, Kondoh Y, Akira M, Ichikado K, Ando M, Honda O, Tomiyama N, Nakamura H. Acute interstitial pneumonia: thin-section CT findings in 36 patients. Radiology. 1999 Jun:211(3):859-63 [PubMed PMID: 10352616]
Level 2 (mid-level) evidenceSuda T, Kaida Y, Nakamura Y, Enomoto N, Fujisawa T, Imokawa S, Hashizume H, Naito T, Hashimoto D, Takehara Y, Inui N, Nakamura H, Colby TV, Chida K. Acute exacerbation of interstitial pneumonia associated with collagen vascular diseases. Respiratory medicine. 2009 Jun:103(6):846-53. doi: 10.1016/j.rmed.2008.12.019. Epub 2009 Feb 1 [PubMed PMID: 19181509]
Level 2 (mid-level) evidenceBonaccorsi A, Cancellieri A, Chilosi M, Trisolini R, Boaron M, Crimi N, Poletti V. Acute interstitial pneumonia: report of a series. The European respiratory journal. 2003 Jan:21(1):187-91 [PubMed PMID: 12570127]
Level 3 (low-level) evidenceAvnon LS, Pikovsky O, Sion-Vardy N, Almog Y. Acute interstitial pneumonia-Hamman-Rich syndrome: clinical characteristics and diagnostic and therapeutic considerations. Anesthesia and analgesia. 2009 Jan:108(1):232-7. doi: 10.1213/ane.0b013e318188af7a. Epub [PubMed PMID: 19095855]
Level 2 (mid-level) evidenceAcute Respiratory Distress Syndrome Network, Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The New England journal of medicine. 2000 May 4:342(18):1301-8 [PubMed PMID: 10793162]
Level 1 (high-level) evidenceARDS Definition Task Force, Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun 20:307(23):2526-33. doi: 10.1001/jama.2012.5669. Epub [PubMed PMID: 22797452]
Robinson DS, Geddes DM, Hansell DM, Shee CD, Corbishley C, Murday A, Madden BP. Partial resolution of acute interstitial pneumonia in native lung after single lung transplantation. Thorax. 1996 Nov:51(11):1158-9; discussion 1164-9 [PubMed PMID: 8958902]
Level 3 (low-level) evidence