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Cryptogenic organizing pneumonia (COP), previously known as bronchiolitis obliterans organizing pneumonia (BOOP), is a significant complication after allogeneic hematopoietic SCT (HCT). However, the pathogenesis of this complication has not yet been elucidated. Therefore, we identified the pre-transplant risk factors for the development of COP/BOOP using the Japan transplant registry database between 2005 and 2009. Among 9550 eligible recipients, 193 experienced COP/BOOP (2%). HLA disparity (odds ratio (OR) 1.51, P=0.05), female-to-male HCT (OR 1.53, P=0.023), and PBSC transplant (OR 1.84, P=0.0076) were significantly associated with an increased risk of COP/BOOP. On the other hand, BU-based myeloablative conditioning (OR 0.52, P=0.033), or fludarabine-based reduced-intensity conditioning (OR 0.50, P=0.0011) in comparison with a TBI-based regimen and in vivo T-cell depletion (OR 0.46, P=0.055) were associated with a lower risk. Of the 193 patients with COP/BOOP, 77 died, including non-relapse death in 46 (59%). Pulmonary failure and fatal infection accounted for 41% (n=19) and 26% (n=12) of the non-relapse death. Allogeneic immunity and conditioning toxicity could be associated with COP/BOOP. Prospective studies are required to elucidate the true risk factors for COP/BOOP and to develop a prophylactic approach.

Bronchiolitis is an inflammatory and potentially fibrosing condition affecting mainly the intralobular conducting and transitional small airways. Secondary bronchiolitis participates in disease process of the airways and/or the surrounding lobular structures in the setting of several already defined clinical entities, mostly of known etiology, and occurs commonly. Primary or idiopathic bronchiolitis dominates and characterizes distinct clinical entities, all of unknown etiology, and occurs rarely. Secondary bronchiolitis regards infections, hypersensitivity disorders, the whole spectrum of smoking-related disorders, toxic fumes and gas inhalation, chronic aspiration, particle inhalation, drug-induced bronchiolar toxicities, sarcoidosis and neoplasms. Idiopathic or primary bronchiolitis defines clinicopathologic entities sufficiently different to be designated as separate disease entities and include cryptogenic constrictive bronchiolitis, diffuse panbronchiolitis, diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, neuroendocrine hyperplasia in infants, bronchiolitis obliterans syndrome in lung and allogeneic hematopoietic cell transplantation, connective tissue disorders, inflammatory bowel disease and bronchiolitis obliterans organizing pneumonia. Most of the above are pathological descriptions used as clinical diagnosis. Acute bronchiolitis, though potentially life threatening, usually regresses. Any etiology chronic bronchiolitis contributes to morbidity and/or mortality if it persists and/or progresses to diffuse airway narrowing and distortion or complete obliteration. Bronchiolitis in specific settings leads to bronchiolectasis, resulting in bronchiectasis.

Bronchiolitis obliterans-organizing pneumonia (BOOP) is an inflammatory and fibrosing disease involving the distal bronchioles, bronchiolar ducts, and alveoli. We studied 91 patients with BOOP. Univariate analysis was used to relate age, sex, smoking, morphology, and expression of immunohistochemical markers CD68, D2-40, CD31, CD34, collagen IV, collagen III, platelet-derived growth factor receptor, and vascular endothelial growth factor (VEGF) with the response to corticosteroid therapy. Seventy-two patients had idiopathic BOOP and 19 secondary BOOP. The median age of the patients was 59.54 years. Most patients were current or former smokers. All cases had a patchy lesion consisting of small buds of fibromyxoid tissue in small bronchioles, bronchiolar ducts, and alveoli. The buds contained collagen and reticulin fibers, fibroblasts, macrophages, mononuclear inflammatory cells, and vessels in different proportions. We found no morphologic differences between primary and secondary BOOP. Patients younger than 38 years and nonsmokers had a significant good response to corticosteroid therapy. Favorable morphologic predictors were the presence of large bronchial plugs and mild inflammatory reaction (P = .093). By immunohistochemistry, the presence of collagen IV with the absence of collagen III, CD68-positive cells and positive VEGF were associated with a good response to corticosteroid therapy. We conclude that age, smoking, localization, and extension of proliferative intrabronchiolar plugs and positive immunostains for CD68, VEGF, and collagen IV with negative collagen III were useful to predict response to corticosteroid therapy and relapse.

Post-radiotherapy bronchiolitis obliterans organizing pneumonia may occur in as many as 2.3% of women receiving radiation therapy for breast cancer. Cough and fever are common symptoms, and a quarter of these women have no symptoms. Latency period is usually within 6 months after completion of therapy but may be as long as 1 year. Pulmonary function is normal or will show slight decreases in vital capacity and diffusing capacity. Chest computed tomography studies show ground-glass opacities with air bronchograms within and outside the radiation field, and there are often peripheral triangular-shaped infiltrates. Management consists of close monitoring of women who have no symptoms or minimal symptoms, and a short-course of corticosteroid therapy for women who have symptoms and extensive bronchiolitis obliterans organizing pneumonia. The prognosis is excellent; there have been no deaths reported.

Background: Many patients are affected by idiopathicbronchiolitis obliterans organizing pneumonia (BOOP). There are several known causes of BOOP, and several systemic disorders have BOOP as an associated primary pulmonary lesion. Numerous agents including cytotoxic and noncytotoxic drugs have the potential to cause pulmonary toxicity. Descriptions of amiodaronerelated BOOP continue to be reported throughout the world. Case Report: We reported a patient with original clinical presentation who developed recurrent sustained ventricular tachycardia (SVT) despite the presence of implantable cardioverter-defibrillator (ICD), hypoxaemia and interstitial pneumonitis in both lung bases. After percutaneous transluminal coronary angioplasty, he developed bronchiolitis obliterans organizing pneumonia (BOOP). Conclusions: To our knowledge, such complications after percutaneous coronary procedure in patients with amiodarone therapy for arrhythmia prophylaxis, are not very frequent in literature.

Background: BOOP is an inflammatory pulmonary disorder consisting of organized polypoid granulation tissue in the distal airways extending into the alveolar ducts and alveoli. Clinical manifestations of BOOP include fever, cough, dyspnea on exertion, and fatigue. Patients with severe BOOP require hospitalization. The mainstay of BOOP treatment is high dose corticosteroids. Many patients relapse and require long term corticosteroids, often in combination with another immunosuppressant. Significant morbidity and disability may be associated with both the diagnosis of BOOP and the toxicities of treatment. The mortality rate of BOOP has been estimated to be about 5%. Radiation Therapy (RT) is an important component in the treatment of breast cancer (Breast Ca). Beginning in 1995, reports of BOOP occurring in Breast Ca RT patients began to appear in the medical literature. From 1995 to the present, 43 case study reports described 121 Breast Ca RT patients who developed BOOP within one year of their RT. From 1999 to 2011, seven epidemiological studies were published that suggested that the incidence of BOOP in Breast Ca RT patients was in the range of 2% to 3%. Objectives: The primary objective of this study was to determine if internet sources of Breast Ca information targeted to Breast Ca patients include BOOP information in their description of RT risks. The secondary objective was to determine if general medical websites conveyed BOOP/Breast Ca RT risk information. Methods: Eight websites specifically targeted to Breast Ca patients were reviewed. Sponsors of these websites included the US government, Breast Ca advocacy groups, and medical organizations. Seven general medical websites that contained BOOP/Breast Ca RT information were also reviewed. Results: There was no mention of BOOP in any of the websites targeted to Breast Ca patients. The websites included those from the National Cancer Institute, American Cancer Society, American Society of Therapeutic Radiology and Oncology, Susan G. Komen, and BreastCancer.org. The internet search identified seven general medical websites that did include information about the risk of BOOP from Breast Ca RT. Discussion: It is perplexing that none of the eight website sources for Breast Ca patients included any mention of the risk of BOOP associated with Breast Ca RT, whereas seven general medical internet sources did disclose this information. This disparity raises important issues and questions. The majority of BOOP/Breast Ca RT reports were published in pulmonology journals. Is this information being disseminated to providers of Breast Ca treatment? Many of the Breast Ca information websites stated that their information was up to date and was reviewed by leading Breast Ca physicians, so it remains an enigma that the BOOP/RT association was not disclosed. The lack of any information about BOOP and Breast Ca RT may indicate Breast Ca physician unawareness. An alternative explanation for this finding may be that these physicans are aware of the BOOP/RT association, but they believe that the rarity of BOOP diagnoses justifies omitting this information in internet-based information sources. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-11-02.

the healthcare providers in recent travelers or immigrants with respiratory manifestations from endemic areas. For clinicians or pulmonologists, detailed interrogations of travel history to endemic areas are critical to manage this entity. The larvae can cause airway inflammation, while migrating adult worms can cause mechanical airway obstruction. This article provides a comprehensive review of both helminthic and protozoal infestations that affect the respiratory system, particularly the lungs, including roentgenographic and clinical presentations, diagnostic tests, and therapeutic methods. Abstract

The etiology of bronchiolitis obliterans organizing pneumonia (BOOP) remains controversial. While it has been reportedly associated with several connective tissue disorders, there are only rare reports of BOOP associated with systemic lupus erythematosus (SLE). Herein, we report a 56-year-old female patient who presented with dyspnea on exertion, cough, fever, and joint pain of her left wrist and fingers as initial symptoms. Laboratory tests revealed positivity for anti-nuclear antibody, anti-Ro, and anti-double strand DNA antibody. In this case, the patient with SLE had respiratory illness as the initial symptom due to BOOP in the absence of clear etiology. The diagnosis of BOOP was confirmed by thoracic surgery biopsy. Her respiratory symptoms and radiologic findings significantly improved following prednisolone treatment.

A 63 year-old man presented with fever, cough, sputum and tachypnea. The latter deteriorated rapidly. A thoracic computed tomography (CT) scan revealed bilateral reticular shadows appearance and quickly spread around two lungs. Notably, CMV PCR was also negative. However, based on inclusion bodies found in lung tissue transbronchial biopsy (TBLB), the diagnosis of CMV pneumonia was confirmed. Lung biopsy showed bronchiolitis obliterans organizing pneumonia (BOOP). Following ganciclovir and steroid treatment, he made a gradually recovery and was discharged seven days later. This case demonstrated that CMV pneumonia may associate with bronchiolitis obliterans organizing pneumonia in an immunocompetent patient.

Acute lower respiratory infections are a leading cause of morbidity and death in all age groups worldwide. The clinical spectrum of syndromes associated with infections involving the lower respiratory tract includes laryngotracheitis, acute bronchitis, bronchiolitis, influenza, exacerbations of chronic bronchitis, and pneumonias. Most infectious pathogens involved in lower respiratory infections are viral, followed by bacterial, fungal, and parasitic. Globally, influenza, respiratory syncytial virus, and parainfluenza viruses cause substantial morbidity and mortality. Streptococcus pneumoniae is leading bacterial agent and can result in otitis media, acute bacterial rhinosinusitis, pneumonia, and invasive disease (bacteremia, meningitis, and/or infective endocarditis). Other important syndromes involving the respiratory system include cavitary lung diseases, tuberculosis-like pneumonias, bronchiectasis, and pleural diseases. Diseases of the chest wall are discussed in chapter: Neck and Thoracic Infections , including empyema necessitates, thoracic actinomycosis, and necrotizing infections of the chest wall. Interstitial lung diseases comprise a plethora of diseases that include infectious, inflammatory, and autoimmune causes. Considering infectious and noninfectious causes of lower respiratory tract infections is crucial. For example, cryptogenic organizing pneumonia (previously bronchiolitis obliterans organizing pneumonia or BOOP) can manifest with persistent or episodic fever, chills, and decreased appetite, cough, and respiratory failure associated with persistent or migratory pulmonary infiltrates. However, aspiration pneumonitis due to macroaspiration of gastrointestinal contents often manifests similarly as cryptogenic organizing pneumonia).

Pulmonary pathologists were aware of cases of idiopathic interstitial pneumonia (IIP) that morphologically did not fit Liebow's classification scheme. These cases were labeled as "cellular interstitial pneumonia" or "chronic interstitial pneumonia not otherwise specified." The term nonspecific interstitial pneumonia (NSIP) was first used in relation to a pattern of lung interstitial inflammation seen in association with human immunodeficiency virus (HIV) infection. In 1994 NSIP was used to indicate a group of subacute or chronic interstitial pneumonias characterized morphologically by interstitial inflammation or fibrosis or both, with preservation of the lung architecture and the absence of typical findings for any of the other main categories of IIP (mainly usual interstitial pneumonia, desquamative interstitial pneumonia, and bronchiolitis obliterans organizing pneumonia). Although these patients presented with "nonspecific" lung histology (categorized as cellular and fibrotic variants), and with a broad spectrum of associated clinical conditions, such as connective tissue diseases (CTDs), environmental exposure, and previous acute lung injury, they showed some peculiar clinical aspects, including favorable response to corticosteroid treatment and overall good prognosis.The clinical and radiographic profiles were better defined in the last decade. The NSIP pattern is the histological background of a subacute/chronic interstitial pneumonitis that may be observed in many conditions, including CTD, drug-induced lung disease, hypersensitivity pneumonitis, slowly healing diffuse alveolar damage (DAD), relapsing organizing pneumonia, occupational exposure, immunodeficiency (mainly HIV infection), graft versus host disease (GVHD), familial pulmonary fibrosis, immunoglobulin G4 (IgG4)-related sclerosing disease, with or without overlap features with Rosai-Dorfman disease, multicentric Castleman disease, and myelodysplastic syndrome. Rarely, NSIP is the histology recognized in patients with idiopathic interstitial pneumonitis, in whom efforts to find potential causative exposures are futile. This entity occurs mostly in middle-aged, never-smoker women, with a likely association with an autoimmune background. High-resolution computed tomographic (HRCT) scans typically demonstrate ground-glass attenuation with a bibasilar distribution, or in the fibrotic variant, ground-glass attenuation along with reticular lines and traction bronchiectasis. The prognosis is good compared with idiopathic pulmonary fibrosis (IPF), and therapeutic options include mainly corticosteroids and immunosuppressive agents. Recently a more precise definition of clinical profiles and radiographic findings of idiopathic NSIP allows consideration of less invasive diagnostic procedures (bronchoalveolar lavage, transbronchial lung biopsy). Better understanding of pathogenetic mechanisms might widen the therapeutic horizon giving a role to new therapeutic options in more severe cases.

Hypersensitivity pneumonitis (HP) is a pulmonary disease with symptoms of dyspnea and cough resulting from the inhalation of an allergen to which the subject has been previously sensitized. The diagnosis of HP most often relies on an array of nonspecific clinical symptoms and signs developed in an appropriate setting, with the demonstration of interstitial markings on chest radiographs, serum precipitating antibodies against offending antigens, a lymphocytic alveolitis on BAL, and/or a granulomatous reaction on lung biopsies. The current classification of HP in acute, subacute, and chronic phases is now challenged, and a set of clinical predictors has been proposed. Nonspecific interstitial pneumonitis, usual interstitial pneumonia, and bronchiolitis obliterans organizing pneumonia may be the sole histologic expression of the disease. Presumably, like in idiopathic interstitial pneumonia, acute exacerbations of chronic HP may occur without further exposure to the offending antigen. New offending antigens, such as mycobacteria causing hot tub lung and metalworking fluid HP, have recently been identified and have stimulated further research in HP.

Almost all mitochondrial proteins are encoded in the nuclear DNA and synthesized in the cytosol as pre-proteins. There is a protein translocase located in the mitochondrial outer membrane that transports mitochondrial pre-proteins into mitochondria. The central component of this translocase of the outer mitochondrial membrane (TOMM) complex is TOMM40, and TOMM5 is one of three small subunits associated with TOMM40. Translocase of outer mitochondrial membrane 5 homolog ( Tomm5–/–) knockout mice demonstrated an unexpected lung-specific phenotype characterized by widespread intra-alveolar fibrosis. Although TOMM5-deficient mice tested normal in a very broad range of phenotyping assays, they displayed histopathological lesions in the lung that were consistent with those reported in humans with cryptogenic organizing pneumonia (COP), which is also known as bronchiolitis obliterans organizing pneumonia (BOOP). The lesions had a patchy distribution in the lung and were characterized by the presence of intraluminal fibrogenic buds consisting of fibroblasts and myofibroblasts embedded in a loose connective tissue matrix that occupied the lumina of alveoli and alveolar ducts, with preservation of underlying alveolar architecture. In addition to macrophages, which were numerous in affected and surrounding alveoli, eosinophils comprised the most common and widespread inflammatory cell. Taken together, the findings in Tomm5–/–mice provide yet another example of the value of histopathology as a baseline assay in high-throughput phenotyping systems.

Propylthiouracil (PTU) therapy is associated with a variety of adverse reactions, among the most rare being interstitial pneumonia. To date, this has been reported in four Asian patients with autoimmune hyperthyroidism. Here we describe a Caucasian woman who developed a bronchiolitis obliterans organizing pneumonia (BOOP)-like interstitial pneumonia after PTU administration for amiodarone-induced thyrotoxicosis.The patient was a 68-year-old woman who had been treated with amiodarone for chronic atrial fibrillation starting in May 2004. She had been a heavy smoker with a history of hypertension but no dust exposures. In October 2006, amiodarone was stopped after she developed thyrotoxicosis. In January 2007 serum thyroid-stimulating hormone (TSH) was 0.01 mIU/L (0.35-4.94) and free T4 was 17.5 pg/mL (7 to 15). She was initially started on methimazole and then changed to PTU after she developed pruritus. She developed severe dyspnea 9 months after starting PTU. At the time she was also taking warfarin, enalapril, and sotalol. Chest X-ray showed diffuse interstitial peripheral opacities and transbronchial lung biopsy revealed subacute lung injury with organizing pneumonia with hyperplasia of the alveolar type 2 pneumocytes, and characteristics of BOOP-like interstitial pneumonia. Signs and symptoms progressively improved after PTU discontinuation as confirmed at X-ray and computed tomography (CT) scan of the chest and by respiratory function tests. She has been recurrence free for 4 years after stopping PTU.This woman of Caucasian ancestral origin developed BOOP-like interstitial pneumonia after PTU treatment for apparent amiodarone-induced thyrotoxicosis, with resolution of her lung disease after stopping PTU. Tests for TSH receptor antibodies, thyroid peroxidase antibodies, and antinuclear cytoplasmic autoantibody were negative. Thyroid ultrasound was consistent with thyroiditis without nodules.PTU-associated interstitial pneumonia is not limited to patients of Asian origin or those with autoimmune thyroid disease. PTU must be withdrawn in the presence of respiratory symptoms and documented interstitial pneumonia. X-ray films, CT-scan, respiratory function tests, and lung biopsy are needed to diagnose PTU-induced interstitial pneumonia with certainty and to monitor the evolution of the disease after PTU discontinuation.

Idiopathic CD4 lymphopenia (ICL) is an immunodeficiency disorder of unclear etiology. Here we describe a heterozygous dominant-negative missense mutation (codon 22 GGC→GTC; V22G) of the signaling adaptor protein Uncoordinated 119 (Unc119) in an ICL patient. The patient is a 32-year-old female with < 300 CD4 T cells/μL and with a history of recurrent sinusitis/otitis media, frequent episodes of shingles, a widespread fungal nail infection, fungal dermatitis, oral herpetic lesions, and bronchiolitis obliterans organizing pneumonia after 2 episodes of bacterial pneumonia. The patient's cells have reduced response to TCR stimulation, with impairment in both localization and enzymatic activation of the lymphocyte-specific kinase (Lck) resulting in decreased cell proliferation. Transduction of the mutant Unc119 but not wild-type Unc119 into normal T cells reproduces the signaling and proliferation defects. The mutation disrupts the Unc119-Lck interaction which is normally needed for stimulation of the Lck catalytic activity by TCR. The mutant protein also causes mislocalization of Lck to Rab11+ perinuclear endosomes. The mutation is not present in 2 other patients with ICL, patients with secondary CD4 lymphopenia or 60 healthy subjects. The V22G mutation of Unc119 represents a novel genetic defect in ICL.

We present a case of a 58-year-old man who experienced Bronchiolitis obliterans organizing pneumonia after a 3-month exposure to polyester powder paint. Mineralogical analysis by transmission electron microscopy of a pulmonary sample and the polyester powder paint he was exposed to showed the presence of titanium dioxide nanoparticles in both. We suggest that exposure to titanium dioxide nanoparticles should be added to the etiology of Bronchiolitis obliterans organizing pneumonia.

Summary Background: Heparin induced thrombocytopenia (HIT) is a serious complication associated with heparin use. HIT usually develops between 5–14 days after starting heparin. Delayed-onset HIT can still occur 9–45 days after heparin had been discontinued. In patients with delayed HIT, the patient might be admitted to the hospital for new thrombosis and reexposure to heparin further worsens the patient’s condition. Case Report: Our patient is a 71-year old female readmitted for worsening dyspnea 2 weeks after she was discharged from the hospital. On her previous hospitalization, she was diagnosed with bronchiolitis obliterans organizing pneumonia (BOOP). She had received prophylactic doses of LMWH. Dyspnea was initially thought to be secondary to CHF exacerbation secondary to atrial fibrillation with rapid ventricular response. She was started on a heparin. However, the patient’s clinical condition deteriorated and she needed to be intubated. Her platelet counts also decreased rapidly. After CT angiography of the chest showed pulmonary embolism, HIT was strongly considered. All forms of heparin were discontinued and argatroban was started. However, the patient did not improve and she subsequently expired on the 7th hospital day. Heparin-induced antibodies came back positive that same day. Conclusions: HIT is an immune-mediated disorder characterized by formation of antibodies against heparin-platelet factor 4 complex. The major clinical presentation of HIT is arterial and venous thrombosis. Once HIT is suspected, immediate cessation of any form of heparin is needed. Alternative anticoagulation must be started. Early treatment decreases the incidence of new thrombosis and stroke, and improves survival and cost savings.

The basic histopathological pattern of organizing pneumonia (OP) is well recognized, but the contexts in which it is encountered continue to increase. In parallel with an appreciation of new causes and associations of OP, an understanding of OP in the spectrum of lung injury and repair has evolved. There is an increasing array of HRCT manifestations of OP, some of which have only recently been described. This article concentrates on new concepts surrounding OP and highlights newly described imaging patterns.

Bronchiolitis obliterans organizing pneumonia (BOOP) is a chronic respiratory disease. Although the pathogenesis of BOOP is still incompletely understood, BOOP is responsive to steroids and has a good prognosis. In our five pigs with chronic postweaning multisystemic wasting syndrome (PMWS), typical BOOP lesions were revealed. All five porcine lungs showed typical intraluminal plugs, and porcine circovirus type 2 (PCV2) was identified. They also exhibited similar pathologic findings such as proliferation of type II pneumocytes and myofibroblasts (MFBs), extracellular collagen matrix (ECM) deposition, and fragmentation of elastic fibers. MFBs migration correlative molecules, for instance, gelatinase A, B and osteopontin, appeared strongly in the progressing marginal area of polypoid intraluminal plugs of fibrotic lesion. These molecules colocalized with the active MFBs. Both gelatinase activity and intercellular level of active MFBs were significantly increased (). Porcine chronic bronchopneumonia leads to BOOP and it is associated with PCV2 persistent infection. Swine BOOP demonstrates similar cellular constituents with human BOOP. Perhaps their molecular mechanisms of pathogenesis operate in a similar way. Thus we infer that the swine BOOP can be considered as a potential animal model for human BOOP associated with natural viral infection. Moreover, it is more convenient to obtain samples.

Summary Background Cryptogenic organizing pneumonia (COP) is a rare disease, and its diagnosis requires histological confirmation. The objective of our study was to describe the findings of the thoracic high-resolution computed tomography (HR-CT) and bronchoalveolar lavage (BAL) in patients with confirmed COP and evaluate the complementary diagnostic use of BAL and thoracic HR-CT. Methods Patients recorded in the registry of interstitial pulmonary diseases between 1991 and 2008 were located and the COP patients selected. Results We identified 21 patients with histological confirmation of COP. The median age was 58.0 ± 15.9 years, and 61.9% of patients were female. The most frequent thoracic HR-CT profile was patchy infiltrate (71.4%), followed by parenchymatous consolidation (42.9%). The most frequent BAL profile was mixed alveolitis (62%) with lymphocyte predominance, a CD4/CD8 index of 0.4 and foamy macrophages. The effectiveness of transbronchial biopsy was 66.6%. The diagnostic utility of Poletti’s BAL criteria gives us a specificity of 88.8%, although the sensitivity obtained was low. The specificity of certain HR-CT profiles is 99%. In addition, we observed a complementary use of the HR-CT and the BAL. Conclusions The imaging findings and BAL could be useful for patients with appropriate clinical presentation and for those whose transbronchial biopsy is negative or for whom a confirmatory biopsy cannot be performed.

An acute exacerbation is the development of acute lung injury, usually resulting in acute respiratory distress syndrome, in a patient with a pre-existing fibrosing interstitial pneumonia. By definition, acute exacerbations are not caused by infection, heart failure, aspiration or drug reaction. Most patients with acute exacerbations have underlying usual interstitial pneumonia, either idiopathic or in association with a connective tissue disease, but the same process has been reported in patients with fibrotic non-specific interstitial pneumonia, fibrotic hypersensitivity pneumonitis, desquamative interstitial pneumonia and asbestosis. Occasionally an acute exacerbation is the initial manifestation of underlying interstitial lung disease. On biopsy, acute exacerbations appear as diffuse alveolar damage or bronchiolitis obliterans organizing pneumonia (BOOP) superimposed upon the fibrosing interstitial pneumonia. Biopsies may be extremely confusing, because the acute injury pattern can completely obscure the underlying disease; a useful clue is that diffuse alveolar damage and organizing pneumonia should not be associated with old dense fibrosis and peripheral honeycomb change. Consultation with radiology can also be extremely helpful, because the fibrosing disease may be evident on old or concurrent computed tomography scans. The aetiology of acute exacerbations is unknown, and the prognosis is poor; however, some patients survive with high-dose steroid therapy.

Alloimmune lung syndromes (allo-LS), including idiopathic pneumonia syndrome, bronchiolitis obliterans syndrome, and bronchiolitis obliterans organizing pneumonia, are severe complications after hematopoietic stem cell transplantation (HSCT). In our cohort of 110 pediatric patients, 30 had allo-LS (27.3%), 18 with idiopathic pneumonia syndrome and 12 with bronchiolitis obliterans syndrome. Multivariate analysis showed that respiratory viral infection early after HSCT is an important predictor for the development of allo-LS (P

A 50 year-old man presented with five months of progressive cough and dyspnea, followed by the acute onset of fever and hypoxemic respiratory failure. Open lung biopsy was notable for pulmonary capillaritis with bronchiolitis obliterans organizing pneumonia. Creatine kinase was normal, and aldolase was mildly elevated. There was no history of muscle weakness or rashes. Testing for anti-PL-7 antibodies was positive, and a diagnosis of the antisynthetase syndrome was made. This is the first reported case of pulmonary capillaritis in association with the PL-7 antisynthetase syndrome. Our case highlights the importance of testing for antisynthetase antibodies in patients presenting with pulmonary capillaritis, even in the absence of characteristic skin rashes or overt muscle weakness.

Bronchiolitis obliterans (BO) or bronchiolitis obliterans organizing pneumonia (BOOP) is one of manifestations of graft-versus-host disease (GVHD), a complication of hematopoietic stem cell transplantation (HSCT). Recently there are reports about thoracic air-leakage syndrome (TALS), but real incidence, clinical course, and implications of TALS remain unclear. Retrospective review of 18 TALS patients among 2,177 patients who received allogeneic HSCT between January 2000 to July 2007 was done. Clinical manifestations, treatments, and outcomes of TALS were reviewed. The incidence of TALS was 0.83% (18/2,177). The onset of TALS was mean 425.9+/-417.8 days (60-1,825 days) after HSCT, and the duration was mean 16.3+/-21 days (2-90 days). The most common types of TALS were spontaneous pneumothroax (n=14), followed by subcutaneous emphysema (n=6), pneumomediastinum (n=5), interstitial emphysema (n=2), and pneumopericardium (n=1). TALS persisted in six patients, who died during the same hospitalization. The 12 patients recovered from TALS, but only 2 survived, while others died due to aggravation of GVHD. TALS may complicate BO/BOOP and be an initial manifestation of BO/BOOP. TALS is hard to be resolved, and even after the recovery, patients die because of aggravation of GVHD. We suggest specifically in HSCT patients, when once developed, TALS seems hard to be cured, and as a result, be related to high fatality.

We describe a patient with clinical, radiological and pathological features of bronchiolitis obliterans organizing pneumonia. Investigation showed that this was likely to have been a delayed consequence of inhalation of nitric acid fumes (containing nitrogen dioxide) after a fire. This case shows that thorough investigation of the aetiology is important not only in clinical management but also in ensuring patients benefit from appropriate work injury compensation.

Bronchiolitis obliterans organizing pneumonia (BOOP) and acute respiratory distress syndrome (ARDS) are two clinically and histologically distinct syndromes sharing the presence of an inflammatory and fibrotic component. Apoptosis via the Fas/Fas ligand (FasL) pathway plays an important role in the development of acute lung injury and fibrosis characteristic of these and other pulmonary inflammatory and fibrotic syndromes. We evaluated the role of apoptosis via the Fas/FasL pathway in the development of pulmonary inflammation and fibrosis in reovirus 1/L-induced BOOP and ARDS. CBA/J mice were intranasally inoculated with saline, 1 × 106 (BOOP), or 1 × 107 (ARDS) PFU reovirus 1/L, and evaluated at various days postinoculation for in situ apoptosis by TUNEL analysis and Fas/FasL expression. Our results demonstrate the presence of apoptotic cells and up-regulation of Fas/FasL expression in alveolar epithelium and in infiltrating cells during the inflammatory and fibrotic stages of both reovirus 1/L-induced ARDS and BOOP. Treatment of mice with the caspase 8 inhibitor, zIETD-fmk, inhibited apoptosis, inflammation, and fibrotic lesion development in reovirus 1/L-induced BOOP and ARDS. However, CBA/KlJms-Faslpr-cg/J mice, which carry a point mutation in the Fas cytoplasmic region that abolishes the ability of Fas to transduce an apoptotic signal, do not develop pulmonary inflammation and fibrotic lesions associated with reovirus 1/L-induced BOOP, but still develop inflammation and fibrotic lesions associated with reovirus 1/L-induced ARDS. These results suggest a differential role for the Fas/FasL apoptotic pathway in the development of inflammation and fibrotic lesions associated with BOOP and ARDS.

Late-onset non-infectious pulmonary complications (LONIPCs) that arise beyond 3 months after allogeneic hematopoietic SCT include bronchiolitis obliterans (BO), bronchiolitis obliterans with organizing pneumonia (BOOP) and idiopathic pneumonia syndrome (IPS). We retrospectively analyzed the incidence and outcome of LONIPCs among pediatric hematopoietic SCT recipients. We included 97 patients who survived for more than 3 months among the 114 who underwent allogeneic hematopoietic SCT between April 1997 and May 2007. Of the 97 enrolled patients, 10 (10.3%) developed LONIPCs at a median of 187 days after hematopoietic SCT (range, 123-826 days). Of the 10 patients with LONIPCs, eight had BO and two had IPS. Multivariate analysis showed that the onset of LONIPCs was associated with high-risk underlying disease and extensive chronic GVHD (hazard ratio, 5.42 (95% confidence interval, 1.36-21.7) and hazard ratio, 11.7 (95% confidence interval, 2.40-57.1), respectively). Only two patients responded to therapy with steroids and six of the 10 patients died. The 5-year OS rate was significantly lower among patients with, than without LONIPCs (28.0 vs 87.2%, P=0.000). Considering that we are lacking optimal therapies for LONIPCs, strategies aimed at the prevention of LONIPCs should be attempted.

Human metapneumovirus (hMPV) is associated with respiratory tract infections among children and adults. Because hMPV induces significant morbidity and mortality in the elderly, a model of hMPV infection in aged BALB/c mice was established. Young (8 weeks old) and aged (18 months old) mice were intranasally inoculated with hMPV. The infected mice showed respiratory dysfunction, as measured by plethysmography, a marked loss in weight (up to 24%), and severe histopathological abnormalities including bronchiolitis obliterans organizing pneumonia. However, clinical severity was far higher in the aged mice, and none of the young infected mice died. Although virus replication in the lung was greater in the older mice, clearance of virus was not delayed compared to young mice. Production of virus-specific antibody as well as neutralizing antibody was lower. Gamma interferon and monocyte chemotactic protein-1 levels in bronchoalveolar lavage fluid were significantly lower in older mice, whereas interleukin-6 and interleukin-4 levels were significantly higher. We observed by flow cytometry a significant increase in the CD4 + T lymphocytes ( P < 0.05) of the aged mice and no difference in CD8 + T-cell recruitment to the respiratory tract between the two groups. The present study investigated the effects of aging on the immunopathogenesis of hMPV infection and suggests that CD4 + T lymphocytes, the cytokine response, or a defect in humoral response may be associated with the increased disease severity observed in the aged mice.

Purpose: To evaluate factors associated with radiation-induced bronchiolitis obliterans organizing pneumonia (BOOP) syndrome after breast-conserving therapy. Methods and materials: A total of 702 women with breast cancer who received radiotherapy after breast-conserving surgery at seven institutions between July 1995 and December 2006 were analyzed. In all patients, the whole breast was irradiated with two tangential photon beams. The criteria used for the diagnosis of radiation-induced BOOP syndrome were as follows: (1) radiotherapy to the breast within 12 months, (2) general and/or respiratory symptoms lasting for >or=2 weeks, (3) radiographs showing lung infiltration outside the radiation port, and (4) no evidence of a specific cause. Results: Radiation-induced BOOP syndrome was seen in 16 patients (2.3%). Eleven patients (68.8%) were administered steroids. The duration of steroid administration ranged from 1 week to 3.7 years (median, 1.1 years). Multivariate analysis revealed that age (>or=50 years; odds ratio [OR] 8.88; 95% confidence interval [CI] 1.16-67.76; p = 0.04) and concurrent endocrine therapy (OR 3.05; 95% CI 1.09-8.54; p = 0.03) were significantly associated with BOOP syndrome. Of the 161 patients whose age was >or=50 years and who received concurrent endocrine therapy, 10 (6.2%) developed BOOP syndrome. Conclusions: Age (>or=50 years) and concurrent endocrine therapy can promote the development of radiation-induced BOOP syndrome after breast-conserving therapy. Physicians should carefully follow patients who received breast-conserving therapy, especially those who are older than 50 years and received concurrent endocrine therapy during radiotherapy.

We evaluated risk factors of radiation pneumonitis (RP) after whole breast irradiation following breast-conserving surgery. Four hundred and seventy-two cases underwent whole breast irradiation with tangential field following breast-conserving surgery in our hospital, between January 2005 and April 2007. Of these cases, we performed statistical analyses for 423 breasts of 413 patients, using a pulmonary dose-volume histogram. Patient characteristics, treatment regimens and irradiation methods were included as variables in the analyses on risk factors of RP. As a result, 89 breasts of 84 cases (21%) were diagnosed with RP. The version 3.0 of the NCI Common Terminology Criteria for Adverse Events was used to evaluate the grade of pneumonitis : 77 cases (18.2%) were diagnosed as Grade 1 RP, 10 cases (2.3%) as Grade 2, and 2 cases (0.5%) as Grade 3. Multivariate analysis indicated that the significant risk factors for RP were central lung distance (CLD) (>1.8 cm) and the short axis length of the radiation field. The incidence of radiationinduced bronchiolitis obliterans organizing pneumonia (BOOP) syndrome significantly correlated only with CLD. The lung volume within the radiation field was shown to be a significant risk factor for RP and radiation-induced BOOP syndrome.

Se presentan 4 casos de pacientes ingresados entre 2001 y 2005 en una unidad geriatrica de agudos hospitalaria con diagnostico de presuncion de bronquiolitis obliterante con neumonia organizada (BONO). En esos pacientes, ante la dificultad de la realizacion de la biopsia transbronquial, con diversidad de presentacion clinica, se realizo el diagnostico de sospecha de BONO sobre la base de los hallazgos clinicos, radiologicos y la respuesta favorable a tratamiento empirico con corticoides. Se realiza una revision clinica, radiologica y terapeutica de esa afeccion en el anciano.

Resume Le Rituximab est un anticorps monoclonal chimerique anti-CD20, dont la toxicite pulmonaire reste exceptionnelle. De nombreux tableaux cliniques peuvent etre observes, pneumopathie interstitielle, hemorragie intra-alveolaire, syndrome de detresse respiratoire aigue. Trois observations de pneumopathie organisee (PO) auparavant appelee bronchiolite obliterante avec pneumopathie organisee (BOOP) ont ete rapportees. Nous avons observe deux cas chez les 25 patients que nous avons traites par Rituximab. L’une est survenue chez une patiente traitee pour une polyarthrite rhumatoide l’autre chez une patiente traitee pour une maladie de Castleman, Le caractere parfois asymptomatique comme dans une de nos observations, nous semble devoir justifier, avant la readministration de Rituximab, la realisation d’une radiographie pulmonaire.

Bei einer 28-jahrigen Patientin mit zunehmender Dyspnoe wurden auf der Thoraxrontgenaufnahme und in der hochauflosenden CT (HRCT) homogen verteilte monomorphe miliare Fleckschatten von ca. 2 mm Durchmesser nachgewiesen. Die histologische Sicherung und der klinische Verlauf ergaben eine kryptogen organisierende Pneumonie, die sich bildmorphologisch ungewohnlicherweise nur mit miliaren Knotchen manifestierte.

Potentially fatal lung toxicity occurs in 12-20% of leukemic patients treated with cytarabine especially at intermediate to high doses, usually presenting as noncardiogenic pulmonary edema (NCPE). Anecdotally the association between cytarabine and the onset of bronchiolitis obliterans organizing pneumonia (BOOP) has been reported. We describe here three cases of patients affected by acute myeloid leukemia (AML) treated with chemotherapeutic regimens including high dose cytarabine, who developed early onset of fever, mild dyspnea, moderate hypoxemia on arterial blood gas analysis and lung infiltrates documented by high-resolution computerized tomography (HRCT), with a more indolent behaviour and a benign clinical outcome, compared with similar cases previously reported in the literature. Our cases widen the spectrum of clinical features of cytarabine-related toxicity in leukemic patients.

Azathioprine and 6-mercaptopurine (6-MP) are effective in inflammatory bowel disease (IBD). However, between 10% and 29% of patients treated with these drugs are forced to stop therapy due to side effects. Pulmonary toxicity due to azathioprine/6-MP has been reported infrequently. We describe 3 patients who developed severe, noninfectious pulmonary toxicity within 1 month after the initiation of azathioprine or 6-MP for the treatment of IBD colitis (2 Crohn's disease and 1 ulcerative colitis). All patients presented with dyspnea, cough, and fever after initiation of azathioprine/6-MP. Evaluation for infectious etiologies, including bronchoscopy (3/3 patients) and open-lung biopsy (2/3 patients) was negative. Histopathologic examination of the lung biopsies revealed bronchiolitis obliterans organizing pneumonia in one, and usual interstitial pneumonitis in another patient. Cessation of purine analog therapy resulted in clinical improvement in all 3 cases. Azathioprine/6-MP-related pulmonary toxicity is a rare but serious side effect, and it is important for clinicians to have a high index of suspicion for this adverse reaction which occurs within 1 month after initiation of treatment for IBD.

IntroductionA rare but serious complication of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy is a lung injury syndrome commonly referred to as a drug-induced interstitial lung disease (ILD). It has a typical clinical presentation of rapidly progressive acute or subacute dyspnea and a histopathology of diffuse alveolar damage (DAD). The incidence, severity, and risk factors for EGFR TKI-induced ILD remain poorly understood. Whether concurrent chemotherapy increases its risk is also unclear. The primary focus of this blinded review was to determine the incidence of ILD leading to death in 1059 TRIBUTE patients randomized to chemotherapy plus erlotinib or placebo.MethodsAll fatal serious adverse events (SAEs) were reviewed by an independent three-person panel composed of a medical oncologist, radiologist, and pulmonologist not associated with the study and without knowledge of treatment assignment. Fatal respiratory SAEs were identified and assigned to one of four potential attributions: progressive cancer, concurrent illness, drug-induced ILD, or other toxicities not related to ILD. Each panel member first made an independent assignation; then each case was discussed jointly. If needed, consensus was reached by vote.ResultsFatal SAEs were reported in 80 of 1059 patients (7.6%): 53 of 526 patients on erlotinib (10.1%) and 27 of 533 on placebo (5.1%) (p < 0.05). Consensus assignation for 41 fatal respiratory SAEs was as follows: cancer, 18 (44%); concurrent illness, 15 (37%); other toxicities not related to ILD, five (12%); ILD, three (7%). All three ILD cases occurred in the erlotinib arm (3/526; 0.6%). The one biopsy-confirmed case of ILD revealed bronchiolitis obliterans organizing pneumonia, a histopathologic finding that has not previously been reported. All three cases of fatal ILD had a typical clinical presentation of acute or subacute onset of dyspnea with rapid progression to respiratory failure.ConclusionsThis independent blinded analysis of the TRIBUTE study identified fatal ILD in 0.6% of cases treated with the combination of erlotinib plus chemotherapy, possibly higher than previous reports of EGFR TKIs alone in the non-Japanese population. Fatal ILD alone does not fully account for the imbalance in fatal SAEs observed in TRIBUTE. EGFR TKI-induced fatal ILD typically presents with acute or subacute dyspnea with rapid progression and a typical histopathology of diffuse alveolar damage both consistent with the acute respiratory distress syndrome, but can also be associated with a histopathology of bronchiolitis obliterans organizing pneumonia. Further studies designed to better understand the underlying pathophysiology and risk factors for ILD are needed.

Bronchiolitis obliterans organizing pneumonia (BOOP) is a diffuse infiltrative pulmonary disorder that has an insidious onset. The patient often presents with flu-like symptoms and radiological findings showing bilateral patchy infiltrates. Histological features show fibromyxoid connective tissue plugs that are evenly spaced in small distal airways and alveolar spaces. Treatment for BOOP is corticosteroid therapy. Critical care nurses must be cognizant of BOOP as a differential diagnosis for patients for whom antibiotic therapy has not resolved symptoms.

Bronchiolitis obliterans organizing pneumonia (BOOP) is a physiopathologic syndrome associating suggestive clinical and imaging features with histopathologic studies showing buds of connective tissue in the lumen of the distal pulmonary airspace.The aim of the study is a retrospective review of all patients with BOOP diagnosed in the Pulmonology Unit of Coimbra Hospital Centre (CHC) between 2000 and 2005.Eleven cases (6 female and 5 male) with mean age 54.8 years were diagnosed. Ten patients were non-smokers and one was an ex-smoker. The mean duration of symptoms was 62.1 days with the initial symptoms dyspnea (8), cough (7), fever (5) and weight loss (2). Nine patients had been given multiple antibiotics, crackles were heard in 6, fever was detected in 6 and dyspnea in 5. Chest X-ray showed bilateral alveolar opacities in 6, focal consolidation in 3, multiple bilateral nodular opacities in 1 and linear opacities in 1. Lung function, performed in 7 patients, showed a reduction in the diffusion capacity in 5. BAL was performed in 8, and all revealed an increase in the percentage of lymphocytes, with low CD4/CD8 in 4. Diagnosis was obtained by pulmonary biopsy performed by TBLB (7), VATS (2) and TTLB (1). Systemic corticosteroids were given in 9 patients. Evolution was favourable in 10 and one patient died.The authors emphasise the time symptoms took to develop, the failure of multiple antibiotics, agreement between symptoms and imaging with those published in the literature, the increased lymphocytes in the BAL, the usefulness of TBLB and the good response to corticosteroids. Resumo: A bronquiolite obliterante com pneumonia organizada (BOOP) é uma entidade clinicopatológica que associa clínica e imagiologia sugestivas à evidência de cilindros de tecido conjuntivo no lúmen dos espaços aéreos distais.Procedeu-se à análise retrospectiva dos casos de BOOP diagnosticados no Serviço de Pneumologia do Centro Hospitalar de Coimbra (CHC) entre 2000 e 2005.Foram diagnosticados 11 casos (6 doentes do sexo feminino e 5 do masculino); média de idades de 54,8 anos; 10 não fumadores e 1 ex-fumador; tempo médio de evolução de 62,1 dias; os sintomas iniciais foram dispneia (8), tosse (7), febre (5) e emagrecimento (2); 9 doentes cumpriram antibioterapia prévia; as alterações do exame físico eram: crepitações à auscultação do tórax (6), febre (6) e dispneia (5); a telerradiografia do tórax mostrou opacidades alveolares difusas bilaterais (6), opacidade alveolar focal unilateral (3), nódulos pulmonares múltiplos bilaterais (1) e padrão intersticial difuso bilateral (1); o EFR foi realizado em 7 doentes, apresentando baixa DLCO/VA em 5; o LBA foi realizado em 8 doentes, apresentando todos alveolite linfocítica e CD4/CD8 baixo em 4; o diagnóstico foi obtido por BPTB (7), VATS (2) e BPTT (1). Foi instituída corticoterapia sistémica em 9 doentes; a evolução foi favorável em 10; um doente faleceu.Os autores destacam o tempo de evolução dos sintomas até ao diagnóstico, a falência de múltiplos antibióticos, a concordância dos sintomas e alterações radiológicas com os habitualmente descritos na literatura, a alveolite linfocitica no LBA, a rentabilidade da BPTB como técnica de diagnóstico e a boa resposta à corticoterapia. Key-words: BOOP, Palavras-chave: BOOP

Bronchiolitis obliterans (BO) and bronchiolitis obliterans organizing pneumonia (BOOP) are late-onset non-infectious pulmonary complications (LONIPCs) following allogeneic hematopoietic stem cell transplantation (HSCT). In the present study 10 of 197 conventionally prepared stem cell recipients developed BOOP after 365 days and 6 patients developed BO 333 days post-transplant. No BOOP or BO was diagnosed following T-cell depletion (p

Background: Although organizing pneumonia (OP) is a common pathological finding, studies including a substantial number of patients with idiopathic forms from a unique center and a long follow-up are rare. Objectives: To determine patients with cryptogenic forms of organizing pneumonia (COP), in order to characterize their clinical course, to identify predictive factors for relapse and to assess their effect on outcome. Methods: For a 19-year period, all histopathological reports from a community teaching hospital were reviewed, and OP was found in 210 lung specimens belonging to 197 patients. Results: Thirty-three (17%) patients presented cryptogenic forms and 32 of them (97%) responded to steroid therapy. At follow-up, 14 patients presented no relapses (no-relapse group, NR) and 18 (56%) presented relapses (relapsing group, RG) that resolved with ulterior treatment. Multifocal opacities on chest X-ray (RG 83% vs. NR 36%, p = 0.02) appeared to be a predictor for relapse. Patients with relapses showed a shorter time span to chest X-ray normalization (RG 8 ± 8 weeks vs. NR 13 ± 9 weeks, p = 0.09) that became significant in patients with 3 or more relapses (multiple-relapse group, MR, 4 ± 2 weeks vs. NR 13 ± 9 weeks, p < 0.04). Although the initial prednisone dose was similar in patients with relapsing forms, its maintenance was shorter than in patients without relapses, showing a trend to significance (RG 4 ± 3 weeks, NR 7 ± 6 weeks, p = 0.09). Lower levels of lactate dehydrogenase and γ-glutamyltransferase, although always within the normal range, were found in patients with relapsing forms. Conclusion: COP is a specific but infrequent form of OP with a good response to steroid therapy. Relapses are frequent and typical characteristics of COP which resolved with ulterior treatment. Multifocal opacities on chest X-ray and a shorter maintenance of the initial steroid dose may increase the risk of relapse.

Objective: Primary graft dysfunction (PGD) causes significant mortality and morbidity after lung transplantation. The objectives of the study were to describe theclinicaland histological sequelaeof PGD.Methods:Histologyofall patientsreceivingsingle-lungtransplantation 1999—2004 (n = 181) was reviewed. PGD was defined as diffuse radiological infiltration of the lung allograft occurring within the first 72 h postoperatively. Results: One patient died intra-operatively. PGD was recorded in 63% (n = 113) of 180 consecutive transplant recipients. Patients with PGD had a worse 90-day postoperative mortality (14% versus 3%, p = 0.03) and 3-year survival (55% versus 77%, p = 0.003). Freedom from bronchiolitis obliterans syndrome was similar in both groups. The maximal FEV1 was significantly lower in patients with PGD, median 54% (quartiles 48—61%) predicted; compared to patients without PGD, median 59% (quartiles 54—69%) predicted (p = 0.003). There was a significant linear trend in the declineofmaximalFEV1withthepresenceandincreasingseverityofradiographicinfiltrate(p = 0.004).Duringfollow-up,patientswithPGDwere more likely to demonstrate diffuse alveolar damage or bronchiolitis obliterans organizing pneumonia (p = 0.009 and p = 0.01, respectively). Histological findings of diffuse alveolar damage correlated closely with extent of radiological infiltration (p < 0.0001). Conclusions: Transplant recipient survival, lung function, and histological findings of diffuse alveolar damage appear to be closely correlated with the appearance and severity of PGD. # 2007 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Summary Background Organizing pneumonia (OP) is a distinct histopathologic lesion that occurs in a variety of clinical contexts. There have been occasional reports of OP occurring in patients with hematologic malignancies. Study objectives To examine the association of OP with hematologic malignancies and to assess the clinical course of affected patients. Design A retrospective review of our institutional experience of unexplained OP developing in patients with hematologic malignancies. Setting Tertiary care, referral medical center. Patients We identified 6 patients with a verified histopathologic diagnosis of OP and antecedent or concomitant diagnosis of a hematologic malignancy from the Mayo Clinic database (1995–2003). Clinical, radiologic, and outcome data were abstracted from records. Results Underlying hematologic disorders included lymphoma (2), acute leukemia (2), cutaneous T-cell lymphoma (1), and myelodysplastic syndrome (1). OP was diagnosed by surgical lung biopsy in 4 and bronchoscopic biopsy in 2. Four of the 6 patients had previously been exposed to chemotherapeutic agents, two had not. Three of the 6 patients had bone marrow transplantation prior to development of OP. Five patients were treated with prednisone and all experienced symptomatic improvement with documented radiologic resolution in 4. One patient experienced symptomatic and radiologic resolution with observation alone. Three patients ultimately died from complications of their underlying hematologic disorder and 1 patient died of unknown causes. Two patients were alive without respiratory complaints more than 1 year after lung biopsy. Conclusions OP occurs in patients with underlying hematologic malignancies who may or may not have been treated with chemotherapy and responds favorably to corticosteroid therapy.

Background: Because reports of bronchiolitis obliterans organizing pneumonia (BOOP) are lacking from the Middle East, we conducted a retrospective review of of all histopathologically proven cases of BOOP over a 10-year period at three tertiary care hospitals in Riyadh and describe the clinical features and outcome. Methods: Charts at the three hospitals were searched using a specific code for BOOP or cryptogenic orga-nizing pneumonia (COP). Lung specimens had to show histological proof of BOOP with a compatible clinical picture. Chest radiographs and high-resolution CT scans were reviewed. Results: Twenty cases of biopsy-proven BOOP had well-documented clinical and radiographic data. There were 11 males and 9 females (mean age, 58 years; range, 42-78). The clinical presentation of BOOP was acute or subacute pneumonia-like illness with cough (85%), fever (70%) dyspnea, (85%) and crackles (80%). The most frequent radiological pattern was a bilateral alveolar infiltrate. The most common abnormality on pulmonary function testing (n=14) was a restrictive pattern (11 patients). Most patients (70%) had no underlying cause (idio-pathic BOOP). Other associations included thyroid cancer, rheumatoid arthritis, syphilis and Wegner′s granulo-matosis. Ten patients (50%) had a complete response to steroids, 6 (30%) had a partial response and 3 (15.8%) with secondary BOOP had rapid progressive respiratory failure and died. Conclusion: The clinical presentation of BOOP in our patients is similar to other reported series. A favorable outcome occurs in the majority of cases. However, BOOP may occasionally be associated with a poor prognosis, particularly when associated with an underlying disease.