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Bronchiolitis Obliterans

Bronchiolitis obliterans – a severe pulmonary condition with concentric fibrous transformation of the submucosal layer within the small airways (bronchioles) resulting in lumen obliteration. The condition is usually caused by host-versus-draft disease. The clinical course is characterized by deterioration in pulmonary function with poor response to treatment.


Presentation

BO course varies in severity and time of onset. It can be mild in onset and deteriorate slowly as well as start acutely with severe symptoms and decline of lung function in days. The symptoms of BO appear at any day between 80 and 700 days after HSCT [10] [11] [12] [13], and include dry cough (in 60-100% of patients), shortness of breath (50-70%) and wheezing (40%). 20% of patients report cold-like symptoms. Approximately 20% of patients are completely asymptomatic, however, show decreased pulmonary function on testing. Fever is absent. All the symptoms are nonspecific.

Fever
  • Abstract We report a patient who presented 6 months after orthotopic liver transplantation (OLT) with fever, dyspnea, and pulmonary infiltrates with biopsy-confirmed Pneumocystis jiroveci infection associated with a process of bronchiolitis obliterans[ncbi.nlm.nih.gov]
  • Abstract A 42-year-old renal transplant recipient was admitted with fever, anorexia, malaise, nonproductive cough, and dyspnea of 1-week duration. Multiple cultures of blood, sputum, and urine were negative.[ncbi.nlm.nih.gov]
  • The plant is widely used in traditional medicine for wound healing, inducing lactation, relief of urinary disorders, as an antidiabetic cure and also fever reduction.[ncbi.nlm.nih.gov]
  • Abstract A 61-year-old female presented with a dry cough and fever 4 months after tangential radiation therapy (RT) following conserving surgery for breast cancer.[ncbi.nlm.nih.gov]
  • Abstract A 14-year-old girl who was known to have a seizure disorder and on lamotrigine treatment was admitted to the hospital, with a history of rash, fever and cough.[ncbi.nlm.nih.gov]
Fatigue
  • Fatigue and wheezing in the absence of a cold or asthma may also be noted. [1] [2] [3] Symptoms generally progress slowly over weeks to months. [3] Last updated: 10/28/2016 Bronchiolitis obliterans is not thought to be inherited.[web.archive.org]
  • People with obliterative bronchiolitis suffer from shortness of breath, wheezing, fatigue and night sweats, among other symptoms. It's an irreversible disease, and it can be life-threatening in severe cases.[remedydaily.com]
  • We ask about general symptoms (anxious mood, depressed mood, fatigue, pain, and stress) regardless of condition. Last updated: January 31, 2019[patientslikeme.com]
  • We ask about general symptoms (anxious mood, depressed mood, fatigue, pain, and stress) regardless of condition. Last updated: May 12, 2019[patientslikeme.com]
Weight Loss
  • May 23, 2013, 12:07 PM EDT Law360, New York (May 23, 2013, 12:07 PM EDT) -- Researchers have reported bronchiolitis obliterans in populations ranging from the builders of boat hauls to Taiwanese women who used a natural weight loss remedy.[law360.com]
  • BOOP presents clinically with initial “flulike” symptoms, followed by progressive dyspnea (shortness of breath), cough, fever, and weight loss. “Crackling” can be heard within the chest using a stethoscope.[accessscience.com]
  • Symptoms For The People says the symptoms of popcorn lung include: - Dry cough - Shortness of breath that gets worse after physical exertion - Wheezing - Fatigue - Fever - Night sweats - Weight loss These symptoms are closely related to those of a respiratory[remedydaily.com]
  • Fever and weight loss are common. Physical examination demonstrates crackles in the lungs in most patients, and wheezing is present in about one-third. Pulmonary function studies demonstrate restrictive dysfunction and hypoxemia.[healthcentral.com]
Camping
  • Gazourian L 1 , Ash S 2 , Meserve EEK 3 , Diaz A 2 , Estepar RSJ 4 , El-Chemaly SY 2 , Rosas IO 2, 5 , Divo M 2, 5 , Fuhlbrigge AL 2, 5 , Camp PC 5, 6 , Ho VT 7 , Bhatt AS 8 , Goldberg HJ 2, 5 , Sholl LM 3 , Washko GR 2 .[ncbi.nlm.nih.gov]
Cough
  • Affected people may experience a dry cough, shortness of breath, and/or wheezing.[web.archive.org]
  • Author information 1 Pulmonary Institute, Kaplan Medical Center, Rehovot, Israel. daniel_s@clalit.org.il Abstract Mycobacterium kansasii disease was diagnosed in an 85-year-old woman admitted to the hospital for cough and gradually worsening breathlessness[ncbi.nlm.nih.gov]
  • Abstract A 42-year-old renal transplant recipient was admitted with fever, anorexia, malaise, nonproductive cough, and dyspnea of 1-week duration. Multiple cultures of blood, sputum, and urine were negative.[ncbi.nlm.nih.gov]
  • Symptoms include a dry cough, shortness of breath, wheezing and feeling tired. These symptoms generally get worse over weeks to months.[en.wikipedia.org]
  • Abstract A 61-year-old female presented with a dry cough and fever 4 months after tangential radiation therapy (RT) following conserving surgery for breast cancer.[ncbi.nlm.nih.gov]
Dyspnea
  • Here, we report the case of a 6-year-old child with recurrent dyspnea since the age of 3, who showed signs and symptoms of bronchiolitis obliterans and radiological signs of bronchial wall thickening and air trapping.[ncbi.nlm.nih.gov]
  • Abstract We report a patient who presented 6 months after orthotopic liver transplantation (OLT) with fever, dyspnea, and pulmonary infiltrates with biopsy-confirmed Pneumocystis jiroveci infection associated with a process of bronchiolitis obliterans[ncbi.nlm.nih.gov]
  • Abstract A 42-year-old renal transplant recipient was admitted with fever, anorexia, malaise, nonproductive cough, and dyspnea of 1-week duration. Multiple cultures of blood, sputum, and urine were negative.[ncbi.nlm.nih.gov]
  • A 60-year-old male patient suffered from mild exertional dyspnea, wheezing, and systemic blisters. He was diagnosed with paraneoplastic pemphigus (PNP) with follicular lymphoma in the pancreas head and pelvic cavity.[ncbi.nlm.nih.gov]
  • A 27-year-old female developed progressive dyspnea after SJS induced by taking amoxicillin at the age of 10. Finally, she died of exacerbation of type II respiratory failure after 17 years from clinically diagnosed as having BO.[ncbi.nlm.nih.gov]
Dry Cough
  • Abstract A 61-year-old female presented with a dry cough and fever 4 months after tangential radiation therapy (RT) following conserving surgery for breast cancer.[ncbi.nlm.nih.gov]
  • Affected people may experience a dry cough, shortness of breath, and/or wheezing.[web.archive.org]
  • Symptoms include a dry cough, shortness of breath, wheezing and feeling tired. These symptoms generally get worse over weeks to months.[en.wikipedia.org]
  • In most cases, gradual onset of shortness of breath and dry cough are symptoms of BOOP/COP. Oral steroids, such as prednisone, are the most common treatment for BOOP/COP.[lung.org]
  • Symptoms of bronchiolitis obliterans include: Dry cough Shortness of breath Fatigue and wheezing in the absence of a cold or asthma Dry cough and shortness of breath are worsened on exertion in patients with ‘Bronchiolitis obliterans’.[yourlawyer.com]
Persistent Cough
  • BO should be considered in a patient who has persistent cough and dyspnea, especially with a history of fume inhalation or offending drug use.[clinicaladvisor.com]
  • Medical Management Workers should be promptly referred for further medical evaluation if they have persistent cough; persistent shortness of breath on exertion; frequent or persistent symptoms of eye, nose, throat, or skin irritation; abnormal lung function[web.archive.org]
  • At the end of follow-up, 2 patients became symptom-free, 7 patients had infrequent mild cough and preferable general well-being, and 8 patients had persistent cough and wheezing and decreased exercise tolerance.[doi.org]
Exertional Dyspnea
  • A 60-year-old male patient suffered from mild exertional dyspnea, wheezing, and systemic blisters. He was diagnosed with paraneoplastic pemphigus (PNP) with follicular lymphoma in the pancreas head and pelvic cavity.[ncbi.nlm.nih.gov]
  • Evaluation of exertional dyspnea in the active duty patient: The diagnostic approach and the utility of clinical testing. Mil Med. 2002;167:281-288. Roop SA, Niven AS, Calvin BE, Bader J, Zacher LL.[web.archive.org]
  • dyspnea after returning from duty in Iraq or Afghanistan.[doi.org]
  • Progressive cough and exertional dyspnea are what usually prompt the patient to seek medical attention. Chest examination demonstrates fine, dry, inspiratory crackles (Velcro crackles).[merckmanuals.com]
Headache
  • It can also cause nausea, vomiting, headache, drowsiness, delirium and hallucinations in high concentrations.[nationaljewish.org]
  • Relieve Sinus Pressure and Headaches with Accupressure video by Lindsay Rose, Holistic Health Lifestyle Management by Condition Meehan, MD, is a rheumatologist at National Jewish Health.[pinterest.pt]

Workup

The diagnosis of BO is made by compilation of clinical, instrumental and laboratory diagnostic data.

Spirometry, lung volumes measure, diffusing capacity for carbon monoxide (DLCO), and arterial blood gases should be ordered for all patients-recipients of HSCT. Airflow obstruction is characteristical hallmark of BO, however, a test may occasionally show normal values, as some cases report. The BO is further differentiated according to the forced expiratory volume in 1 second (FEV1) measures into mild (FEV1 66–80%), moderate (FEV1 51–65%) and severe (FEV1 50%) forms.

General workup should be ordered to exclude other possible causes of symptoms (i.e. infection) and detect complications of the GVHD. It should include complete blood count (CBC) with differential, blood urea nitrogen (BUN), creatinine, liver function tests (total bilirubin and hepatic transaminases), gammaglobulin and urinalysis.
Of the imaging studies, the high resolution computed tomography (HRCT) may be the most useful. It is of the most value when performed with both inspiratory and respiratory views. An expiratory section may show additional zones of air-trapping not detectable on the inspiratory view and the amount of these findings has been shown to correlate with the severity of disease [14] [15]. Other pathological changes may be revealed on the HRCT such as bronchiectasis, thickened septal lines, mosaic or so-called "tree-in-bud" pattern of attenuation [14]. Chest X-ray is not as useful and frequently will show little to no changes. It may reveal some slight hyperinflation.

Transbronchial biopsy, although frequently performed, may miss the pathological tissue as the involvement pattern of OB is often intermittent and mosaic [5]. The biopsies are done to exclude acute rejection of the graft or missed infection. The biopsy is contraindicated in cases of severe bronchiole obstruction or thrombocytopenia. Video assistance if often required for the definitive OB diagnosis by histological study, which may reveal peribronchial neutrophilic and lymphocytic infiltration and fibrosis with partial or complete obliteration of the lumen. Severe cases may show necrotizing bronchitis or bronchiolitis.

The diagnosis is made by such criteria: persistent pulmonary dysfunction with FEV1 reduced below normal for more than 3 weeks and if other causes (acute allograft rejection, anastomotic complications, stricture, infections) are ruled out.

Hyperlucent Lungs
  • […] bronchioles and alveolar ducts by fibrous granulation tissue induced by mucosal ulceration; the condition may follow inhalation of irritant gases ( see silo-filler's lung ) or may complicate pneumonia; associated with obstructive findings ( see unilateral hyperlucent[medical-dictionary.thefreedictionary.com]
  • The consequences of bronchiolitis obliterans include dyspnea (shortness of breath), obstructive lung disease, atelactasis, bronchiectasis, and unilateral hyperlucent lung.[healthcentral.com]
  • In some instances, they can even develop a form of unilateral hyperlucent lung syndrome, known as Swyer-James Syndrome. Symptoms associated with BO may develop gradually, or they may occur suddenly.[hxbenefit.com]
  • Unilateral hyperlucent lung syndrome in children. J Pediatr 1971 ; 78 : 250 –60. Lang WR , Howden CW, Laws J, et al. Bronchopneumonia with serious sequelae in children with evidence of adenovirus type 21 infection. BMJ 1969 ; 1 : 73 –9.[thorax.bmj.com]
Pulmonary Infiltrate
  • Abstract We report a patient who presented 6 months after orthotopic liver transplantation (OLT) with fever, dyspnea, and pulmonary infiltrates with biopsy-confirmed Pneumocystis jiroveci infection associated with a process of bronchiolitis obliterans[ncbi.nlm.nih.gov]
  • The possibility of bronchiolitis obliterans with organizing pneumonia (BOOP) was considered when pulmonary infiltrate did not respond to conventional antibiotic therapy.[ncbi.nlm.nih.gov]
  • Abstract The present study describes an adult male who has had recurrent episodes of pulmonary infiltrates with severe acute respiratory failure over a period of 10 yrs.[ncbi.nlm.nih.gov]
  • Epler GRMark EJ A 65-year-old woman with bilateral pulmonary infiltrates. N Engl J Med. 1986;3141627- 1635 Google Scholar Crossref 55.[jamanetwork.com]
Bilateral Pulmonary Infiltrate
  • Epler GRMark EJ A 65-year-old woman with bilateral pulmonary infiltrates. N Engl J Med. 1986;3141627- 1635 Google Scholar Crossref 55.[jamanetwork.com]
Pericardial Effusion
  • We describe a case of SLE presenting with shortness of breath, found to have pneumothorax, bilateral nodular infiltrates along with pleural effusions and pericardial effusion.[ncbi.nlm.nih.gov]
Mycobacterium Kansasii
  • Author information 1 Pulmonary Institute, Kaplan Medical Center, Rehovot, Israel. daniel_s@clalit.org.il Abstract Mycobacterium kansasii disease was diagnosed in an 85-year-old woman admitted to the hospital for cough and gradually worsening breathlessness[ncbi.nlm.nih.gov]

Treatment

Only a small amount of data has been received as for improvement of the outcomes in patients with OB with various treatment measures. Immunomodulation and immunosuppression therapy is the mainstay of current views for the treatment options, however, only a few patients have shown reactivity to the therapy.

Corticosteroids are used as a first-line treatment. Prednisone is given at the dose of 1–1.5 mg/kg/day up to 100 mg/day for 4-6 weeks. If patient’s respiratory functions are stabilized, prednisone is tapered and then stopped in 6-12 months. In the cases when no therapeutic effect is achieved with corticosteroids in 1 month, the regimen should be changed to cyclosporine (adjusted to serum level) or azathioprine (2–3 mg/kg/day up to 200 mg/day). Cyclosporine also has shown to prevent development of BO in some cases.

Macrolides have demonstrated some benefit in patients with BO, particularly in those with panbronchitis, probably due to the anti-inflammatory effect of this group of antibiotics.

Despite earlier reports, neither thalidomide nor intravenous immunoglobulin have shown no beneficial therapeutic effect in treatment of BO and GVHD.

The patients on immunosuppressive therapy should also receive prophylaxis for Pneumocystis carinii and Streptococcus pneumoniae at all times, as they are at risk for developing these infections.

Prognosis

Prognosis is usually poor. With appropriate treatment regimen of corticosteroids and immunosuppressants only 8-20% of the patients demonstrate an improvement in pulmonary functions.

Mortality is variable in the available reports, measuring from 14% to 100% in some studies. The mean for mortality rate is 61%. There is an association of rapid decrease in FEV1 with increased mortality.

Etiology

Several etiologies of BO are possible.

The most common cause is a graft-versus-host disease (GVHD) from an organ transplantation procedure. It is primarily caused by type-2 T-helper lymphocytes of the donor and characterized by progressive concentric fibrosis of the small airways. It is rarely seen in autologous type of transplantation. BO from bone marrow transplantation occurs in approximately 9% of patients. BO from stem cell transplantation is much less common. Although BO remains a major life-threatening possible complication in patients after lung transplantation, the procedure itself is greatly improving survival of patients with end-stage pulmonary insufficiency.

The other possible causes include exposure to different toxic materials. Fume-exposure BO occurs after contact with typical acidic toxic fumes (i.e. in silo-fillers). The contact is usually accidental. The disease has a three-period course with two latent phases: during the first few hours and then several days. BO can also result from exposure to mustard gas (i.e. chemical warfare weapon), with one case reported in a man after as much as 14 years after exposure. The symptoms included cough with sputum and shortness of breath. A few cases were described in eastern Asian countries with patients developing toxin-related BO after ingesting the Sauropus androgynus vegetable.

Epidemiology

Due to the lack of standardized criteria for the diagnosis, the reports for incidence of BO vary. Most of the cases are diagnosed clinically by pulmonary function tests showing the pattern of airway obstruction and the histological tests are not performed.

Some studies report 8.3% incidence of BO in 2152 patients-recipients of allogeneic HSCT. In the patients with GVHD the incidence is estimated to be approximately 6-20% in the long-term.

Sex distribution
Age distribution

Pathophysiology

The exact pathophysiology of BO remains unknown. Several hypothesis exist for the chain of events of BO development. One suggests that host bronchiolar epithelial cells act as a target of attack for donor cytotoxic T-cells, which is supported by the association of BO and chronic GVHD. Another possible pathophysiological causing events are recurrent aspiration and subsequent infection due to chronic GVHD and/or a malfunction of local immunoglobulin secretion. Due to the high variability in histopathological results of studies of bronchoalveolar lavage (BAL) cell composition and differences in clinical course, a multifactorial chain of events is supposed to be the pathophysiological underlying cause.

The pathophysiology of the graft rejection is complex, usually involving both alloimmune and non-alloimune pathways. Chronic rejection can be further differentiated as chronic vascular, which is less common and constitutes for atherosclerotic process in the vessels of the lungs, or chronic airway rejection, which is more common and comprises the histological definition of BO. The latter is associated with higher morbidity and mortality.

The resulting concentric fibrotic formation in the bronchiolar submucosa is referred to as constrictive bronchiolitis (CB), or fibrosing bronchiolitis in early literature. It is a chronic process of concentric peribronchilar fibrosis of the tissues surrounding the lumen of the bronchiole, in contrast to growing into the lumen per se. CB is characterized by continuous mural thickening of the submucosal layer, fibrosis of collagen fibers and progressive narrowing of the lumen, eventually leading to stasis of the mucus, chronic inflammation or even complete obliteration.

BO tends to result in inflammation of only membranous bronchioles (small noncartilagenous airways) [7] [8], causing encircling fibrosis and consequent narrowing of the lumen. The extent of muscular level involvement differs depending on the stage of the disease. In early course, it may appear hypertrophic, but later it is prone to atrophy and replacement by fibrous tissue. It has been noted, however, that distal respiratory bronchioles usually remain intact.

Histological pattern of BO also varies in the timely manner of disease progression. Early examination may show inflammation of the submucosal layer of small airways, mainly composed of lymphocytic infiltration and resulting in disturbance of epithelium. The deep ingrowth of fibromyxoid granulation tissue and consequent partial or even complete lumen obliteration follow next. Eventually, granulation tissue may organize and form cicatricle pattern on a histological level [9].

Prevention

Prevention should be focused on early diagnosis and aggressive management of associated conditions.
Decreasing time of allograft ischemia by lowering mechanical ventilation lenght for donors has shown some success in prevention. Blood products exchange and cardiopulmonary shunts should be avoided [16].

Summary

Bronchiolitis obliterans (BO) is a severe pulmonary condition, usually a complication following the organ transplantation procedure. Lungs are the most common solid organs affected by severe rejections [1] [2], however, despite BO remaining a leading cause of death past the first year of lung transplantation [3] [4], the procedure is sometimes the only option for patients with advanced pulmonary disorders and high stages of pulmonary insufficiency. A few rare cases of BO were reported to result from exposure to toxins.

The most prominent clinical manifestation of BO is the deterioration of forced expiratory volume in 1 second (FEV1) with no response to bronchodilators therapy [5] [6]. The functional decrease is a result of small airway obliteration. Patients usually experience following symptoms: dry cough, wheezing, dyspnea and cold-like symptoms, however, there is no fever in OB clinical course. None of the symptoms are specific enough, however.

The diagnosis is usually clinical and made by identifying a decrease in FEV1 while excluding all the other possible causes (i.e. infection). Lung biopsy may not be significantly informative as it can miss the lesion. Histological study will show inflammation of the submucosal layer of small airways, mainly composed of lymphocytic infiltration and disturbance of epithelium. In late stages of the disease the pathological process results in narrowing and obliteration of the airway lumen. The lesions do not extend into the alveoli and are limited to bronchioles.

Chest X-ray is usually non-informative and may only show a slight hyperinflation. High resolution computed tomography (HRCT) is the imaging modality of choice. It should be done both in expiration and inspiration states. HRCT may reveal air-trapping which is not only diagnostic, but also correlates with the severity of BO. General workup should include complete blood count with differential, blood urea nitrogen, creatinine, liver function tests, gammaglobulin and urinalysis to rule out other causes.

Current view on the treatment implies the use of immunosuppression and immunomodulation agents. First-line management is with corticosteroids. If steroids have no effect on pulmonary function improvement, cyclosporine and azathioprine may be introduced.

Patient Information

Bronchiolitis obliterans (BO) is a condition involving the lung’s smallest airways – the bronchioles. It is usually a complication following an organ transplant, as body immune system is reacting to a foreign structures, but rarely can be caused by inhaled toxins, such as poisonous vegetables or warfare chemicals.

The inflammation in the bronchioles results in extensive scarring of these tiny structures and leads to their obliteration. Affected patients usually feel cough and shortness of breath, however, may show no signs or symptoms initially and demonstrate decrease in lung functions only by diagnostic tests. The symptoms may appear in the first months after transplantation or be delayed for years.

For the diagnosis of BO special studies are used to assess lungs functioning, such as spirometry, when patient exhales forcefully into a tube. This helps doctors to measure lungs volumes and obtain an idea of how well they work. Imaging studies may also be done to see the extent of the disease.

BO cannot be cured and the doctors’ efforts are concentrated on slowing the progression and stabilizing the functional state of the lungs. It is important to diagnose BO early as it may be crucial to start therapy as soon as possible to prevent dangerous complications. The medications to decrease immune response of the body such as corticosteroids or immunosuppressant may be used for that. However, the response to treatment is usually not sufficient.

References

Article

  1. Hopkins PM, Aboyoun CL, Chhajed PN, Malouf MA, Plit ML, Rainer SP, Glanville AR. Prospective analysis of 1,235 transbronchial lung biopsies in lung transplant recipients. J Heart Lung Transplant. 2002; 21:1062-7. 
  2. Arcasoy SM, Kotloff RM. Lung transplantation. N Engl J Med. 1999; 340:1081-91. 
  3. Verleden GM. Chronic allograft rejection (obliterative bronchiolitis). Semin Respir Crit Care Med. 2001; 22:551-8. 
  4. Christie JD, Edwards LB, Kucheryavaya AY, Aurora P, Dobbels F, Kirk R, Rahmel AO, Stehlik J, Hertz MI. The Registry of the International Society for Heart and Lung Transplantation: twenty-seventh official adult lung and heart-lung transplant report–2010. J Heart Lung Transplant. 2010; 29:1104-18. 
  5. Estenne M, Maurer JR, Boehler A, Egan JJ, Frost A, Hertz M, Mallory GB, Snell GI, Yousem S. Bronchiolitis obliterans syndrome 2001: an update of the diagnostic criteria. J Heart Lung Transplant. 2002; 21:297-310. 
  6. Estenne M, Hertz MI. Bronchiolitis obliterans after human lung transplantation. Am J Respir Crit Care Med. 2002; 166:440-4. 
  7. Yousem SA, Berry GJ, Cagle PT, Chamberlain D, Husain AN, Hruban RH, Marchevsky A, Ohori NP, Ritter J, Stewart S, Tazelaar HD. Revision of the 1990 working formulation for the classification of pulmonary allograft rejection: Lung Rejection Study Group. J Heart Lung Transplant. 1996; 15:1-15. 
  8. Stewart S, Fishbein MC, Snell GI, Berry GJ, Boehler A, Burke MM, Glanville A, Gould FK, Magro C, Marboe CC, McNeil KD, Reed EF, Reinsmoen NL, Scott JP, Studer SM, Tazelaar HD, Wallwork JL, Westall G, Zamora MR, Zeevi A, Yousem SA. Revision of the 1996 working formulation for the standardization of nomenclature in the diagnosis of lung rejection. J Heart Lung Transplant. 2007; 26:1229-42.
  9. Yousem SA, Duncan SR, Griffith BP: Interstitial and airspace granulation tissue reactions in lung transplant recipients. Am J Surg Pathol 1992, 16:877-84.
  10. Clark JG, Crawford SW, Madtes DK et al. Obstructive lung disease after allogeneic marrow transplantation. Clinical presentation and course. Ann Intern Med 1989; 111: 368–376.
  11. Curtis DJ, Smale A, Thien F et al. Chronic airflow obstruction in long-term survivors of allogeneic bone marrow transplantation. Bone Marrow Transplant 1995; 16: 169–173. 
  12. Chan CK, Hyland RH, Hutcheon MA et al. Small-airways disease in recipients of allogeneic bone marrow transplants. An analysis of 11 cases and a review of the literature. Med (Balt) 1987; 66: 327–340.
  13. Krowka MJ, Rosenow EC III, Hoagland HC. Pulmonary complications of bone marrow transplantation. Chest 1985; 87: 237–246
  14. de Jong PA, Dodd JD, Coxson HO, Storness-Bliss C, Paré PD, Mayo JR, Levy RD. Bronchiolitis obliterans following lung transplantation: early detection using computed tomographic scanning. Thorax. 2006; 61:799-804. 
  15. Bankier AA, Van Muylem A, Knoop C, Estenne M, Gevenois PA. Bronchiolitis obliterans syndrome in heart-lung transplant recipients: diagnosis with expiratory CT. Radiology. 2001; 218:533-9
  16. Lee JC, Christie JD, Keshavjee S: Primary graft dysfunction: definition, risk factors, short- and long-term outcomes. Semin Respir Crit Care Med. 2010; 31:161-71.

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Last updated: 2019-07-11 20:35