How I diagnose and treat organizing pneumonia in hematopoietic cell transplant recipients.

ABSTRACT: Organizing pneumonia (OP) is a known noninfectious pulmonary complication following allogeneic hematopoietic cell transplant (HCT) and represents a significant risk factor for nonrelapse mortality in HCT recipients. Unlike bronchiolitis obliterans syndrome, it is not universally acknowledged as a distinctive pulmonary manifestation of chronic graft-versus-host disease (cGVHD) and, therefore, its diagnostic criteria and management approach are lacking. Given its shared similar clinical features and radiological and histologic findings to OP in the non-HCT population, the diagnostic approach and treatment strategy for OP in HCT recipients is largely adapted from the non-HCT population. In this article, we aim to enhance the understanding of OP within the context of cGVHD following HCT and distinguish its clinical features and treatment strategy from non-HCT counterparts, thereby reinforcing its recognition as a pulmonary manifestation of graft-versus-host disease. We will propose the diagnostic criteria and outline our approach in diagnosis and treatment strategy, highlighting the potential challenges that may arise in each process. Finally, we will discuss knowledge gaps in this field and identify the area of need for future research.

Is acute fibrinous and organizing pneumonia the expression of immune dysregulation?

INTRODUCTION: Acute fibrinous and organizing pneumonia (AFOP) is a recently described histologic pattern of diffuse pulmonary disease. In children, all cases reported to date have been fatal. In this study, we describe the first nonfatal AFOP in a child and review the literature. DESCRIPTION: A 10-year-old boy developed very severe aplastic anemia (VSAA) after being admitted to our hospital with a fulminant hepatic failure of unknown origin. A chest computed tomography scan revealed multiple lung nodules and a biopsy of a pulmonary lesion showed all the signs of AFOP. Infectious workup remained negative. We started immunosuppressive therapy with antithymocyte globulin and cyclosporine to treat VSAA. Subsequent chest computed tomography scans showed a considerable diminution of the lung lesions but the VSAA did not improve until we performed hematopoietic stem cell transplantation 5 months later. CONCLUSIONS: Aplastic anemia is associated with a variety of autoimmune syndromes. The sequence of events in our patient suggests that the hepatic failure, AFOP, and the VSAA may all have been part of an autoimmune syndrome. AFOP could be the result of immune dysregulation in this pediatric case with favorable outcome after immunosuppressive therapy and hematopoietic stem cell transplantation.

[Cryptogenic organizing pneumonia]. / La pneumonie organisée cryptogénique.

Cryptogenic organizing pneumonia (COP) is a distinct clinico-pathologic entity described for the first time by Davison in 1983 and 2 years later by Epler under the name of idiopathic Bronchiolitis Obliterans Organizing Pneumonia (BOOP). It most often presents with the clinical and radiological features of an infectious pneumonia which fails to respond to antibiotic therapy. In this article, we will review the clinical and radiographic features, diagnostic assessment, and the treatment of COP.

Severe acute respiratory failure secondary to acute fibrinous and organizing pneumonia requiring mechanical ventilation: a case report and literature review.

A 27-year-old woman was admitted to our ICU with acute hypoxemic respiratory failure and criteria for ARDS. Despite an F(IO(2)) of 1.0 and a lung protective strategy, the patient died on day 15 without any improvement. The relatives gave consent for post-mortem analysis. The histopathologic study of the lung showed findings typical of an acute fibrinous and organizing pneumonia. Apropos of this case we performed a PubMed search. We found 13 articles, including a total of 29 patients. Acute fibrinous and organizing pneumonia is an unusual cause of acute lung injury. The diagnostic criterion is histopathologic. There is little information regarding the pathophysiology of this illness. Important questions remain regarding this disease, including predisposing factors and management. Patients who require mechanical ventilation have poor outcomes.

[Organizing pneumonia: diagnosis and treatment].

According to current classifications, organizing pneumonia (OP) belongs to the group of diffuse parenchymatous diseases of the lungs. Morphological picture of OP is characterized by the presence of polypoid granulation tissue consisting of proliferating fibroblasts and myofibroblasts in the gap of respiratory bronchioles. In most cases OP is idiopathic. Among the causes, most significant are diffuse diseases of the connective tissue and complications of pharmacotherapy. OP develops more frequently in 50-60-year old males and females. Typical for OP is an acute/subacute course with a clinical picture of bacterial pneumonia. Mean duration of the symptoms to diagnosis is 2-6 months. Roentgenologically, OP often presents with spotted bilateral (less often unilateral) dense consolidation foci of subpleural location; pulmonary volumes are, as a rule, unaffected. OP treatment of choice is administration of glucocorticosteroid drugs. The prognosis of OP is favourable, most of the patients are completely cured by glucocorticosteroids.

Organizing pneumonia primed by high-dose chemotherapy and lung irradiation: two pediatric cases.

A 9-year-old and a 17-year-old male patients affected by metastatic Ewing sarcoma developed an organizing pneumonia after high-dose chemotherapy with autologous peripheral blood stem cell transplantation followed by total-lung irradiation. They were successfully treated with high-dose corticosteroid for 6 months slowly tapered, with a significant clinical and radiologic response. Organizing pneumonia is a nonspecific response to various forms of lung injury such as high-dose chemotherapy and radiotherapy. For this reason, even if rare, has to be considered in children affected by lung metastatic Ewing sarcoma with persisting pulmonary symptoms after peripheral blood stem cell transplantation and total-lung irradiation. This report provides a useful description for the evaluation and treatment of pediatric patients with pulmonary infiltrates after chemotherapy and radiotherapy.

A 69-Year-Old Woman With Ulcerative Colitis and Pulmonary Nodules.

CASE PRESENTATION: A 69-year-old woman with a medical history significant for COPD, ulcerative colitis (UC), and tobacco dependence was referred to a pulmonologist for lung nodules found on routine annual low-dose CT scan for lung cancer screening. Her review of systems was negative for dyspnea, angina, hemoptysis, fever, night sweats, anorexia, and weight loss. She had a successful total proctocolectomy with ileal pouch-anal anastomosis performed 5 years ago because of acute fulminant UC refractory to corticosteroids and biologic agents. Her home medications were albuterol inhaler, umeclidinium, and vilanterol inhalation powder. She denied any history of lung cancers in her family. She was an active smoker and had a 35-pack-year smoking history. She worked as a cashier in a local supermarket and had been doing so for the past 25 years.

[Update 2021: Pulmonary Sequelae of COVID-19 Pneumonia]. / Update 2021: Pulmonale Folgen nach COVID-19-Pneumonie.

Acute COVID-19 pneumonia may result in persistent changes with various imaging and histopathological patterns, including organizing pneumonia and pulmonary fibrosis. In addition, SARS-CoV-2 infection is associated with increased risk of pulmonary vascular endothelialitis and thrombosis. Herein, current findings on pulmonary consequences of COVID-19 with implications for clinical management are summarized based on a selective literature review.

Organizing pneumonia in ALK+ lung adenocarcinoma treated with ceritinib: A case report and literature review.

RATIONALE: Anaplastic lymphoma kinase (ALK) inhibitors have been approved for patients with ALK-rearrangement lung cancer. The effect is superior to the standard first-line therapy of pemetrexed plus platinum-based chemotherapy. However, ALK inhibitors are associated with rare and sometimes fatal adverse events. Organizing pneumonitis (OP) is a rare and serious adverse event usually caused by ceritinib, and it is easily misdiagnosed as infectious pneumonia, metastasis, or cancer progression. PATIENT CONCERNS: A 56-year-old female presented with chest tightness and dyspnea for more than 10 days. She was previously healthy with no significant medical history. Workup including chest computed tomography (CT), pathological examination of a biopsy specimen, and next-generation sequencing was consistent with a diagnosis of IVA ALK-rearrangement lung adenocarcinoma. She was treated with pemetrexed plus platinum-based chemotherapy and crizotinib concurrently, followed by maintenance therapy with crizotinib alone and she had an almost complete response. However, about 26 months after beginning treatment she developed multiple brain metastases. Crizotinib was discontinued and she was begun on ceritinib. After about 3 months the brain metastases had almost complete response. After 5 months of ceritinib, however, multiple patchy lesions appeared in the bilateral upper lungs. DIAGNOSES: Treatment with antibiotics had no effect and blood and sputum cultures are negative. A CT-guided biopsy of the upper lung was performed, and pathological hematoxylin-eosin staining and immunohistochemical studies were consistent with OP. INTERVENTIONS: Ceritinib was discontinued, she was begun on prednisone 0.5 mg/kg orally every day, and regular follow-up is necessary. OUTCOMES: CT of the chest 2 and 4 weeks after beginning prednisone showed the lung lesions to be gradually resolving, and she was continued on prednisone for 2 months and gradually reduced the dose of prednisone every 2 weeks. No related adverse events were occurred in patient. LESSONS: OP must be differentiated from infectious pneumonia, metastasis, or cancer progression. The mechanism of OP is still unknown and needs further research. Biopsy plays a role in making a diagnosis of OP. In our patient, discontinuing ceritinib and treating her with prednisone resulted in a good outcome.

Signal recognition particle (SRP) positive myositis in a patient with cryptogenic organizing pneumonia (COP).

We report of a 46-year-old female patient with cryptogen organizing pneumonia preceding the rare SRP positive necrotising myositis without cardiac involvement and no sign of dysphagia. Myositis showed full regression without oral immune suppression but with extracorporeal treatment, performed as a combined therapy of plasmaexchange and immunoadsorption. After 33-month of treatment, anti-SRP antibodies were not detectable any more.

[Systemic disease with hepatic and pulmonary involvement]. / Systemerkrankung mit Leber- und Lungenbeteiligung.

We discuss the history of a 39 year old woman with multiple patchy consolidations on high - resolution computed tomography in combination with a delayed diagnosis of primary biliary cirrhosis. Further we review the differential diagnostic considerations and step by step diagnostic and therapeutic options. Based on the presentation with symptoms of a mitigated pneumonia at the beginning of the disease, the differential diagnosis of cryptogenic organising pneumonia (CO) is discussed. The diagnosis of COP is often delayed. The theoretic background of primary biliary cirrhosis and the association with pulmonary disease are broadly discussed.

Clinical and radiologic distinctions between secondary bronchiolitis obliterans organizing pneumonia and cryptogenic organizing pneumonia.

BACKGROUND: Bronchiolitis obliterans organizing pneumonia (BOOP) is a distinct pattern of reaction of the lung to injury. It may be idiopathic or secondary to a variety of injuries. The term cryptogenic organizing pneumonia (COP) is used for patients with idiopathic BOOP. In this study we describe clinical and radiologic features of patients with BOOP. METHODS: The medical records of 33 patients with diagnosis of BOOP on surgical lung biopsy over a 10-year time period were reviewed retrospectively. We obtained data on clinical and radiologic manifestations, etiology, and outcome of these patients. RESULTS: Dyspnea was the most common symptom, followed by dry cough and fever. Crackles was the most common physical finding. Mean age at diagnosis of BOOP was 59 years, and 42% were females. The main radiologic manifestation was bilateral patchy consolidation. Most patients had favorable prognosis; however, 17% did not respond to treatment. Female sex was more common in COP than in secondary BOOP (P = .004). Patients with COP had longer symptom duration before the diagnosis than secondary BOOP (P = .01). Patients with secondary BOOP reported fever more frequently, compared to COP (P = .005). Pleural effusion was present in 60% of patients with secondary BOOP, whereas none of the patients with COP had effusion (P = .004). CONCLUSIONS: COP and secondary BOOP have diverse clinical and radiologic manifestations. Patients with secondary BOOP are more symptomatic. Both COP and secondary BOOP patients have good prognosis, and most respond to treatment with corticosteroids or by discontinuing the injurious drug.

[Case of unilateral organizing pneumonia induced by amiodarone pulmonary toxicity].

A 78-year-old man with diabetes mellitus, hyperthyroidism and congestive heart failure was admitted to our hospital because of dyspnea on effort. He had been taking 200 mg/day amiodarone for 2 years, in order to treat a intermitted ventricular tachycardia. His chest X rays showed the appearance of diffuse consolidation in the right lung field. At first severe pulmonary infection was suspected, and he was treated with antibiotics. In spite of the treatment, the chest X-ray findings did not improved. We thought of the possibility of interstitial lung disease, and performed bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB) from the right middle lobe. TBLB revealed the organizing pneumonia (OP). At the same time we observed that he had temporary sinus arrest and entered a stated of shock requiring intubation, temporary pacing and intra-aortic balloon pumping (IABP) . The coronary angiography (CAG) revealed no abnormalities and cardiac function was normal. Within two days his sinus rhythm recovered spontaneously. After cessation of amiodarone and administering steroid therapy, pulmonary shadows resolved quickly. Since there were no laboratory signs of connective tissue or infectious disease such as a normal autoimmune serology, antibody titers against Mycoplasma pneumoniae, Clamydia species, and BAL, TBLB cultures, etc, we considered that unilateral organizing pneumonia and temporary sinus arrest could be induced by amiodarone. The amiodarone pulmonary toxicity (APT) commonly courses pleural effusion and while it may be strictly unilateral, there are often diminutive contralateral foci visible on HR-CT. Steroids should be given for months and tapered prudently, otherwise APT may recur owing to the persistence of amiodarone in lung.

Organizing pneumonia.

Organizing pneumonia (OP) is a histologic term characterized by patchy filling of alveoli and bronchioles by loose plugs of connective tissue. OP may be an incidental finding in lung biopsy specimens or may be found nearby areas of lung involved by other diseases. On other occasions, OP may be the primary cause for pulmonary dysfunction and/or pulmonary symptoms. OP can be either idiopathic (cryptogenic organizing pneumonia, COP) or secondary to underlying disease (secondary organizing pneumonia, SOP). COP typically presents with a prodrome of symptoms of a respiratory illness followed by the insidious onset of dyspnea weeks to months later. The radiological findings typically reveal peripheral consolidation, although ground glass infiltrates or solitary nodules may be seen. The definitive diagnosis of OP requires histology. Open lung biopsy or video assisted thoracoscopy is usually required to obtain specimens large enough for the diagnosis to be made. In some cases, transbronchial biopsy specimens may be adequate for the diagnosis. The treatment of choice for OP includes corticosteroids plus treatment of the underlying disease in cases of SOP. Relapses occur frequently, usually when treatment is withdrawn or tapered. The prognosis is good in most of the cases of COP, whereas in SOP it is dependent on the underlying cause.

Relapsing bronchiolitis obliterans organising pneumonia and chronic sarcoidosis in an atopic asthmatic patient.

Asthma is thought to be a Th2 disease while sarcoidosis is considered a Th1 granulomatous disorder. Organising pneumonia is a histologic pattern of lung injury. When it has no recognisable cause it is defined as cryptogenic organising pneumonia. We herein report the case of a patient with recurrent and steroid sensitive organising pneumonia associated with chronic sarcoidosis in an atopic, moderate persistent asthmatic patient. Each disease has been documented with transbronchial biopsies and recurrence of organising pneumonia was suggested by clinical features and by follow up HRCT which shows distinctive signs even in associated disease. Steroids are the mainstay of therapy for these disorders and especially for the consolidated processes typical of organising pneumonia but prognostic indices for relapse and progression are lacking.

Cryptogenic organizing pneumonia: clinical profile in a series of 34 admitted patients in a hospital in India.

OBJECTIVES: Cryptogenic Organizing Pneumonia (COP) is a relatively rare disorder which is gratifying to treat due to its prompt steroid responsiveness. There have been only 2 case reports on COP from India but no large series entity reported from this country. METHODS: The medical records of all patients with biopsy (histopathology) proven COP admitted in a tertiary care hospital in Mumbai (2000-2005) were retrospectively analyzed. We looked at clinical and radiographic profiles, initial diagnosis and treatment, lag period to starting definitive therapy and steroid responsiveness. RESULTS: When compared to other series of patients with COP, our series showed several similarities and some differences. Distinctive features were the striking female preponderance and the utility of transbronchial biopsies in establishing the diagnosis. Long delays in diagnosis with patients mislabeled as tuberculosis or pneumonia, lead to delays in starting steroids resulting in 21% of our patients continuing to deteriorate. CONCLUSIONS: This comprehensive review of COP, the first of its kind from India, reveals its varied clinical and radiographic spectrum. A high index of suspicion will lead to prompt steroid therapy which will result in better patient outcome.

¿Enfermedad o reacción pulmonar intersticial? Investigar hasta encontrar el origen / Interstitial lung disease or reaction? Investigate until you find the source

La neumonía organizativa es un patrón histológico que puede observarse asociado o reactivo en diferentes patologías.Presentamos el caso de una mujer de 67 años con diagnóstico inicial de neumonía organizada criptogénica, sin respuestaa los glucocorticoides y autoinmunidad negativa. Finalmente, la neumonía organizada resultó ser secundaria a neoplasiahematológica. En estos casos es importante insistir en la anamnesis y realizar los procedimientos necesarios para conseguirel diagnóstico definitivo.(AU)

Organizational pneumonia is a histological pattern that can be observed associated or reactive in different pathologies. Wepresent the case of a 67-year-old woman with an initial diagnosis of organized pneumonia, no response to glucocorticoidsand negative autoimmunity. Finally, organized pneumonia was found to be secondary to hematologic malignancy. In thesecases, it is important to insist on the anamnesis and perform the necessary procedures to achieve the definitive diagnosis.(AU)