Scoping review: The state of research on cryptogenic organizing pneumonia therapeutics.

Cryptogenic organizing pneumonia is a diffuse interstitial lung disease that starts in the alveolar wall and subsequently expands to the alveolar ducts and respiratory bronchioles. Randomized controlled trials are lacking to guide the treatment of cryptogenic organizing pneumonia, so treatment decisions and practice guidelines are often based upon observations from case series or expert clinical opinions. The backbone of treatment involves immunosuppression via corticosteroids. In refractory cases, cytotoxic therapy is considered. The evidence that supports the use of these regimens are limited. The goal of this scoping review is to conduct a systematic search of the literature to determine what regimens have been utilized to treat steroid refractory organizing pneumonia and to characterize the evidence supporting their use.

Cryptogenic Organizing Pneumonia: A Unique Case and Literature Review.

Pneumonia is one of the most common pathologies seen in the inpatient setting. The rapid response to treat febrile patients with infiltrates on chest x-ray has reduced hospital length of stay and hospital costs. However, the automatic reaction to treat all infiltrates and opacities seen on a chest x-ray as pneumonia can be costly. This report presents the case of a patient suspected initially of having pneumonia, who was unresponsive to broad-spectrum antibiotics. A 58-year-old woman presented with dyspnea on exertion and a nonproductive cough. Her chest x-ray showed dense right-sided coalescent opacities encompassing the entirety of the right lung. Flexible bronchoscopy biopsy specimens revealed the cause to be cryptogenic organizing pneumonia. This case highlights the diverse set of pulmonary pathologies that can mimic pneumonia and should be suspected in cases of antibiotic-resistant suspected pneumonia patients.

Cryptogenic organizing pneumonia associated with pregnancy: A case report.

BACKGROUND: Cryptogenic organizing pneumonia (COP), formerly known as bronchiolitis obliterans organizing pneumonia, is an extremely rare disease in pregnancy. In this case, we report on COP diagnosed in recurrent pneumonia that does not respond to antibiotics in pregnant woman. CASE SUMMARY: A 35-year-old woman with no prior lung disease presented with concerns of chest pain with cough, sputum, dyspnea, and mild fever at 11 wk' gestation. She was diagnosed with community-acquired pneumonia and treated with antibiotics; her symptoms improved temporarily. Four weeks after discharge, she was re-admitted with aggravated symptoms. Chest computed tomography demonstrated multifocal patchy airspace consolidation and ground-glass opacities at the basal segments of the right lower lobe, at the lateral basal segment of the lower lobe, and at the lingular segment of the left upper lobe. Bronchoalveolar lavage revealed an increased lymphocyte count and a decreased CD4/CD8 ratio. Prednisolone (0.5 mg/kg/d) was administered for 10 d after the second admission. Dyspnea improved after 3 d of steroid treatment and other symptoms improved on the 5th day of steroid administration. Post-delivery transbronchial lung biopsy further revealed the presence of granulation tissue with fibroblasts in small-bronchiole lumens. CONCLUSION: This case suggests that it is important to differentiate COP from atypical pneumonia in the deteriorated condition despite antibiotic treatment.

Interstitial lung abnormality (ILA) and nonspecific interstitial pneumonia (NSIP).

This review article aims to address mysteries existing between Interstitial Lung Abnormality (ILA) and Nonspecific Interstitial Pneumonia (NSIP). The concept and definition of ILA are based upon CT scans from multiple large-scale cohort studies, whereas the concept and definition of NSIP originally derived from pathology with evolution to multi-disciplinary diagnosis. NSIP is the diagnosis as Interstitial Lung Disease (ILD) with clinical significance, whereas only a part of subjects with ILA have clinically significant ILD. Eventually, both ILA and NSIP must be understood in the context of chronic fibrosing ILD and progressive ILD, which remains to be further investigated.

Clinico-etiological characteristics of organizing pneumonia: A retrospective study.

INTRODUCTION: Organizing pneumonia (OP) is an idiopathic interstitial pneumonia characterized radiologically by the patchy peripheral areas of ground-glass opacities and consolidation. It is commonly associated with a variety of conditions such as connective tissue diseases (CTD), drugs, infections, malignancy, radiation exposure, post-transplant, and other interstitial pneumonia. There are no specific clinical manifestations unless there is an underlying etiology. We present a series of such cases. AIMS AND OBJECTIVES: The aim of the study was to identify the clinical characteristics and etiological spectrum of patients manifesting radiologically with OP pattern. MATERIALS AND METHODS: This was a retrospective analysis of clinico-radiological profile and etiological diagnosis of 23 patients, who had a radiological diagnosis of OP during the period of January 2017-September 2019. RESULTS: Our patients presented with nonspecific symptoms of cough, fever, breathlessness, and occasionally with hemoptysis. The various etiologies identified were CTD (n = 4), infection (n = 2), drugs (n = 4), radiation (n = 1), chronic aspiration syndrome (n = 1), malignancy (n = 2), hypersensitivity pneumonitis (n = 1), and chronic heart failure (n = 2), and in majority (n = 7), no underlying etiology was evident and were labeled as cryptogenic organizing pneumonia. CONCLUSION: OP is an underdiagnosed entity and is associated with numerous diseases varying from pulmonary tuberculosis to malignancy. Identification of the underlying disease process is of paramount importance as it enables the treating physician to implement necessary therapeutic interventions.

[Cryptogenic organizing pneumonia versus secondary organizing pneumonia]. / Kryptogen organisierende Pneumonie versus sekundäre organisierende Pneumonie.

Organizing pneumonia (OP) describes a histological pattern of acute or subacute lung damage. Clinically, patients present with cough, fever, and dyspnea. A distinction is made between idiopathic or cryptogenic organizing pneumonia (COP) and secondary organizing pneumonia (OP). In COP, neither clinical/radiological nor histological causes can be determined. It is classified as an interstitial idiopathic pneumonia (IIP) according to the criteria of the American Thoracic Society (ATS) and the European Respiratory Society (ERS). Secondary organizing pneumonia has a known triggering mechanism, such as infectious agents, certain medications, or concomitant symptoms of other primary pulmonary diseases and diseases of other organ systems. Common to both forms is the histological picture of intra-alveolar mesenchymal buds. These are myofibroblast proliferates that branch out along the alveolar spaces. They are usually accompanied by a moderate interstitial and alveolar, chronic, and macrophage-rich inflammatory cell infiltrate. The most important differential diagnosis is common interstitial pneumonia (UIP). It also shows fibroblast proliferates, which are, however, located in the interstitium. The correct classification of an IIP as a COP by means of clinical, radiological, and histological findings is essential, since the COP, in contrast to the UIP, responds very well to corticosteroids and therefore has an excellent prognosis compared to the UIP. The course of secondary organizing pneumonia depends on the respective underlying disease. Here it is important for the pathologist to correctly identify potential accompanying histological characteristics in order to be able to provide clues to a possible cause of OP.

Cryptogenic Organizing Pneumonia Secondary to Mycoplasma pneumoniae Infection: A Case Report.

Cryptogenic organizing pneumonia (COP), previously known as bronchiolitis obliterans organizing pneumonia (BOOP), is a serious lung disease that can cause significant and long-term damage to the distal respiratory tract. Here we describe an unusual case in which an adult patient with recent mycoplasma pneumonia developed worsening lower airway disease despite initiation of multiple antibiotic therapies, illustrating the immunological effects related to Mycoplasma infections. It is critical that clinicians learn how to recognize early signs of COP in order to tailor appropriate therapy, reduce morbidity, and improve quality of life.

Bronchiolitis obliterans organizing pneumonia as the pulmonary manifestation of lupus: A review of three cases.

OBJECTIVE: Bronchiolitis obliterans organizing pneumonia (BOOP) is a clinico-patho-radiological diagnosis which rarely presents as a pulmonary manifestation of lupus. In this concise report, organizing pneumonia was found as the sole pulmonary manifestation of SLE in different age groups. METHOD: All three patients diagnosed with SLE according to SLICC 2012 classification criteria, were admitted in rheumatology ward of NIMS hospital, Hyderabad, India from May to November, 2018. Their diagnosis of BOOP was either biopsy proven or imaging guided. Review of literature was done with MeSH terms (SLE, BOOP) in PubMed and approximately 10 articles were reviewed including latest of 2019 published in Scientific Reports. RESULT: There were three patients - one juvenile lupus and two adults. Two patients were male and one female. All three patients had SLE with high disease activity. They all had organising pneumonia as pulmonary manifestation with other organ involvement. Juvenile patient had a fatal outcome while the others had a good recovery with steroid and immunosuppressive. CONCLUSION: BOOP is a rare pulmonary manifestation in lupus. It can be diagnosed early with more precision using computerised tomography of lung without waiting for biopsy report. This will result in a better prognosis by rapid initiation of corticosteroid and immunosuppressive treatment.

Organizing pneumonia secondary to influenza infection: Two case reports and a literature review.

BACKGROUND: Organizing pneumonia (OP) is a rare complication of influenza virus infection but scarce data are available. The recognition of this entity is important because require appropriate treatment. METHODS: We report two cases and perform a systematic review on PubMed database. Only cases with histological confirmation of OP and influenza virus positive laboratory test were included. RESULTS: We collected 16 patients. Median age was 52 year, 20% of patients were smokers and 43.8% had not any comorbidity. Influenza A virus infection was diagnosed in 75%. Clinical manifestation consisted on a respiratory deterioration with a median time of appearance of 14 days. Radiological pattern observed was ground-glass opacities with consolidations. Survival was observed in 12 patients (75%). All three patients who did not receive steroid treatment died. CONCLUSION: Physicians must be aware that patients with influenza infection with a torpid course could be developing OP and prompt corticoid therapy should be instaured.

A Case of Dermatomyositis Causing Cryptogenic Organizing Pneumonia.

Cryptogenic organizing pneumonia (COP), also known as idiopathic bronchiolitis obliterans organizing pneumonia (BOOP), is a rare inflammatory condition. It often presents as sequelae of existing chronic inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, and various connective tissue conditions. This case describes a 28-year-old African American female who presented with a complex clinical picture involving chronic inflammatory processes and the pulmonary system. The initial evaluation suggested pneumonia to be the underlying cause of respiratory symptoms; however, ultimately, a diagnosis of BOOP with dermatomyositis was made.

Oxaliplatin-induced bronchiolitis obliterans organizing pneumonia following hyperthermic intraperitoneal chemotherapy.

Oxaliplatin given systemically is associated with pneumonitis in less than 1% of cases. This case report describes acute respiratory failure, due to bronchiolitis organising pneumonia, in a patient with colorectal carcinoma being treated with hyperthermic intraperitoneal chemotherapy which included oxaliplatin and CPT-11 (irinotecan). The clinical course, the lack of an identifiable infectious agent and the complete response to corticosteroids suggested a drug-induced cause. After ruling out CPT-11, oxaliplatin was considered to be the causal agent. The unusual feature of this case was that pneumonitis developed after intraperitoneal administration of oxaliplatin. Oxaliplatin-associated respiratory complications can occur whatever route the drug is administered.

Bronchiolitis obliterans organizing pneumonia after stereotactic ablative radiation therapy for lung cancer: A case report.

Bronchiolitis obliterans organizing pneumonia is an interstitial lung disease rarely occurring after radiotherapy probably due to an activation of autoimmune processes. Most cases have been described after postoperative radiotherapy for breast cancer. Corticosteroids represent the main treatment, prognosis is generally favorable. We described a case of bronchiolitis obliterans organizing pneumonia after stereotactic ablative radiation therapy for a recurrent lung cancer. Antibiotics and steroids were administered to solve the clinical picture. After three years, a new lesion at the right lung was found and treated with stereotactic ablative radiation therapy and concomitant long course of steroids with no recurrence of bronchiolitis obliterans organizing pneumonia. Bronchiolitis obliterans organizing pneumonia is a rare event after radiotherapy with undefined risk factors. In our case, steroids played an important role in management and, maybe, in preventing bronchiolitis obliterans organizing pneumonia recurrence after second course of stereotactic ablative radiation therapy.

[Medical prevention and treatment of radiation-induced pulmonary complications]. / Prévention médicale et traitement des complications pulmonaires secondaires à la radiothérapie.

Radiation-induced lung injuries mainly include the (acute or sub-acute) radiation pneumonitis, the lung fibrosis and the bronchiolitis obliterans organizing pneumonia (BOOP). The present review aims at describing the diagnostic process, the current physiopathological knowledge, and the available (non dosimetric) preventive and curative treatments. Radiation-induced lung injury is a diagnosis of exclusion, since clinical, radiological, or biological pathognomonic evidences do not exist. Investigations should necessarily include a thoracic high resolution CT-scan and lung function tests with a diffusing capacity of the lung for carbon monoxide. No treatment ever really showed efficacy to prevent acute radiation-induced lung injury, or to treat radiation-induced lung fibrosis. The most promising drugs in order to prevent radiation-induced lung injury are amifostine, angiotensin-converting-enzyme inhibitors and pentoxifylline. Inhibitors of collagen synthesis are currently tested at a pre-clinical stage to limit the radiation-induced lung fibrosis. Regarding available treatments of radiation-induced pneumonitis, corticoids can be considered the cornerstone. However, no standardized program or guidelines concerning the initial dose and the gradual tapering have been scientifically established. Alternative treatments can be prescribed, based on clinical cases reporting on the efficacy of immunosuppressive drugs. Such data highlight the major role of the lung dosimetric protection in order to efficiently prevent radiation-induced lung injury.

A Cryptogenic Case of Fulminant Fibrosing Organizing Pneumonia.

Cryptogenic organizing pneumonia (COP) generally responds well to corticosteroids with a favorable outcome. Rare cases of organizing pneumonia are rapidly progressive. Yousem et al. studied pathologic predictors of idiopathic bronchiolitis obliterans organizing pneumonia/COP with an unfavorable prognosis. Beardsley and Rassl proposed the name fibrosing organizing pneumonia (FOP). A 74-year-old female non-smoker presented with a 2-week history of dry cough followed by dyspnea and a fever. The clinical course was fulminant, but we successfully performed bronchoscopy. After the diagnosis of FOP, we treated the patient with mechanical ventilation and high-doses of steroids/immunosuppressants, which improved the disease.

Lung injury pathways: Adenosine receptor 2B signaling limits development of ischemic bronchiolitis obliterans organizing pneumonia.

Purpose/Aim of the Study: Adenosine signaling was studied in bronchiolitis obliterans organizing pneumonia (BOOP) resulting from unilateral lung ischemia. MATERIALS AND METHODS: Ischemia was achieved by either left main pulmonary artery or complete hilar ligation. Sprague-Dawley (SD) rats, Dahl salt sensitive (SS) rats and SS mutant rat strains containing a mutation in the A2B adenosine receptor gene (Adora2b) were studied. Adenosine concentrations were measured in bronchoalveolar lavage (BAL) by HPLC. A2A (A2AAR) and A2B adenosine receptor (A2BAR) mRNA and protein were quantified. RESULTS: Twenty-four hours after unilateral PA ligation, BAL adenosine concentrations from ischemic lungs were increased relative to contralateral lungs in SD rats. A2BAR mRNA and protein concentrations were increased after PA ligation while miR27a, a negatively regulating microRNA, was decreased in ischemic lungs. A2AAR mRNA and protein concentrations remained unchanged following ischemia. A2BAR protein was increased in PA ligated lungs of SS rats after 7 days, and 4 h after complete hilar ligation in SD rats. SS-Adora2b mutants showed a greater extent of BOOP relative to SS rats, and greater inflammatory changes. CONCLUSION: Increased A2BAR and adenosine following unilateral lung ischemia as well as more BOOP in A2BAR mutant rats implicate a protective role for A2BAR signaling in countering ischemic lung injury.

Radiation-Induced Organizing Pneumonia: A Characteristic Disease that Requires Symptom-Oriented Management.

Radiation-induced organizing pneumonia (RIOP) is an inflammatory lung disease that is occasionally observed after irradiation to the breast. It is a type of secondary organizing pneumonia that is characterized by infiltrates outside the irradiated volume that are sometimes migratory. Corticosteroids work acutely, but relapse of pneumonia is often experienced. Management of RIOP should simply be symptom-oriented, and the use of corticosteroids should be limited to severe symptoms from the perspective not only of cost-effectiveness but also of cancer treatment. Once steroid therapy is started, it takes a long time to stop it due to frequent relapses. We review RIOP from the perspective of its diagnosis, epidemiology, molecular pathogenesis, and patient management.

[Clinical manifestations of organizing pneumonia]. / Manifestaciones clínicas de la neumonía en organización.

Organizing pneumonia is a clinical entity asociated with nonspecific symptoms and radiological findings and abnormalities in pulmonary function tests. It is defined by the characteristic histopathological pattern: filling of alveoli and respiratory bronchioles by plugs of granulation tissue. It can be idiopathic (COP) or secondary to other causes (SOP). It is an unusual finding and the clinical and radiographic findings are nonspecific. For specific diagnosis an invasive procedure has to be done, but often empirical treatment is started when there's a clinical suspicion. We describe the clinical characteristics of 13 patients with histological diagnosis of organizing pneumonia. Data was obtained from their medical records. The median age was 76 years and the median time to diagnosis from the onset of symptoms was 31 days. In 10 cases the diagnosis was made by transbronchial biopsy. 8 patients required hospitalization, 4 of them received high doses of steroids and 3 required ventilatory support. One patient died from a cause attributable to this entity and 5 relapsed. Dyspnea, cough and fever were the most frequent symptoms. Most patients had more than one tomographic pattern being the most common ground glass opacities and alveolar consolidation. Nine patients were diagnosed with COP and 4 with SOP. The most frequent underlying cause of SOP was drug toxicity. The clinical characteristics of the reported cases are consistent with previously published series. As an interesting feature, there was a group of patients that needed high doses of steroids and ventilatory support.

Manifestaciones clínicas de la neumonía en organización / Clinical manifestations of organizing pneumonia

La neumonía en organización es una entidad clínica asociada a síntomas y hallazgos radiológicos inespecíficos y anomalías en las pruebas de función pulmonar. El patrón histopatológico característico se define por tapones intra-alveolares de tejido de granulación. Puede presentarse sin una etiología determinada -neumonía en organización criptogénica (COP, cryptogenic organizing pneumonia)- o en otra condición clínica -neumonía en organización secundaria (SOP: secondary organizing pneumonia). Es poco frecuente y las manifestaciones clínico-radiológicas son poco específicas. Para su confirmación se requieren procedimientos invasivos, siendo habitual el tratamiento empírico con esteroides sistémicos ante la sospecha clínica. Se presentan 13 casos con diagnóstico histológico de neumonía en organización describiendo las características clínicas. La mediana de edad fue 76 años y la de tiempo al diagnóstico desde el inicio de los síntomas: 31 días. En 10 casos el diagnóstico fue por biopsia transbronquial (BTB). Ocho pacientes requirieron internación, 4 de ellos recibieron pulsos de esteroides y soporte ventilatorio. Uno falleció por una causa atribuible a la entidad y 5 presentaron recaídas. Disnea, tos y fiebre fueron los síntomas más frecuentes. La mayoría presentó más de un patrón tomográfico, siendo los más habituales vidrio esmerilado y consolidación alveolar. En 9 se realizó el diagnóstico de COP y en 4 de SOP. La causa secundaria en todos los casos fue toxicidad por drogas. Las características clínicas de los casos comunicados son consistentes con las series previamente publicadas. Cabe destacar la necesidad de tratamiento con dosis altas de esteroides y soporte ventilatorio en un grupo de pacientes.

Organizing pneumonia is a clinical entity asociated with nonspecific symptoms and radiological findings and abnormalities in pulmonary function tests. It is defined by the characteristic histopathological pattern: filling of alveoli and respiratory bronchioles by plugs of granulation tissue. It can be idiopathic (COP) or secondary to other causes (SOP). It is an unusual finding and the clinical and radiographic findings are nonspecific. For specific diagnosis an invasive procedure has to be done, but often empirical treatment is started when there’s a clinical suspicion. We describe the clinical characteristics of 13 patients with histological diagnosis of organizing pneumonia. Data was obtained from their medical records. The median age was 76 years and the median time to diagnosis from the onset of symptoms was 31 days. In 10 cases the diagnosis was made by transbronchial biopsy. 8 patients required hospitalization, 4 of them received high doses of steroids and 3 required ventilatory support. One patient died from a cause attributable to this entity and 5 relapsed. Dyspnea, cough and fever were the most frequent symptoms. Most patients had more than one tomographic pattern being the most common ground glass opacities and alveolar consolidation. Nine patients were diagnosed with COP and 4 with SOP. The most frequent underlying cause of SOP was drug toxicity. The clinical characteristics of the reported cases are consistent with previously published series. As an interesting feature, there was a group of patients that needed high doses of steroids and ventilatory support.

LPS-Responsive Beige-Like Anchor Gene Mutation Associated With Possible Bronchiolitis Obliterans Organizing Pneumonia Associated With Hypogammaglobulinemia and Normal IgM Phenotype and Low Number of B Cells.

LPS-Responsive Beige-like Anchor (LRBA) deficiency is a disease which has recently been described in a group of patients with common variable immunodeficiency (CVID) in association with autoimmunity and/or inflammatory bowel disease (IBD)-like phenotype. We here describe a 10-year-old boy who experienced recurrent infections, mainly in the respiratory system, associated with thrombocytopenia and anemia. Immunological workup showed low numbers of B cells and low IgG, but normal IgM levels. In spite of therapeutic doses of antibiotics, antivirals, and antifungal agents, in addition to immunoglobulin replacement therapy, he developed disseminated involvement of both lungs with peripheral nodules; transbronchial lung biopsy revealed possible bronchiolitis obliterans organizing pneumonia (BOOP). Combined homozygosity mapping and exome sequencing identified a homozygous LRBA mutation in this patient (p.Asp248Glufs*2). Such clinical and immunological findings have not been described to date and illustrate the broad and variable clinical phenotype of human LRBA deficiency.

[Cryptogenic organizing pneumonia]. / Pneumopathie organisée cryptogénique.

INTRODUCTION: Organizing pneumonia is a particular type of inflammatory reaction of the lung which gives rise to a clinico-pathological syndrome. It is called "secondary" when a cause such as an infection, a drug toxicity, or a connective tissue disease can be identified, or "cryptogenic" when no cause is identified. The clinical picture is usually characterized by the subacute onset of fever, fatigue, cough and dyspnea, with multiple subpleural areas of consolidation on thoracic imaging. STATE OF THE ART: Organizing pneumonia is characterised by the presence of buds of endoalveolar connective tissue. These result from an injury to the alveolar epithelium, followed by the deposition of fibrin in the alveolar spaces, and the migration of fibroblasts which produce a myxoid endoalveolar matrix. A remarkable feature of organizing pneumonia is the complete disappearance of these endoalveolar buds with corticosteroid treatment, in sharp contrast with what is seen in pulmonary fibrosis. The clinical response to corticosteroids is usually prompt and excellent. Relapses are frequent but usually benign. PERSPECTIVES AND CONCLUSION: As the clinical, imaging and pathological characteristics of organizing pneumonia are now well established, many questions remain unanswered, such as the mechanisms involved in the complete reversibility of the pulmonary lesions, and the role of steroid-sparing treatments such as immunomodulatory macrolides.