Organizing pneumonia secondary to influenza infection: Two case reports and a literature review / Neumonía organizativa secundaria a infección por el virus de la gripe: comunicación de 2 casos y revisión de la literatura

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

ANTECEDENTES: La neumonía organizada (OP, por sus siglas en inglés) es una complicación poco frecuente de la gripe. El reconocimiento de esta entidad es importante porque requiere un tratamiento adecuado. MÉTODOS: Comunicamos 2 casos y realizamos una revisión sistemática en PubMed, incluyendo casos con confirmación histológica de OP y prueba de laboratorio positiva para gripe. RESULTADOS: Se recogieron 16 pacientes. La edad media fue de 52 años, el 20% eran fumadores y el 43,8% no tenían comorbilidades. El virus de la gripe A se identificó en el 75% de los casos. La presentación clínica consistió en un deterioro respiratorio, con una mediana de aparición de 14 días. El patrón radiológico más común fue opacidades en vidrio esmerilado con consolidaciones. Sobrevivieron 12 pacientes (75%). Los 3 pacientes que no recibieron tratamiento esteroideo murieron. CONCLUSIÓN: Los clínicos deben tener en cuenta que los pacientes con gripe con un curso tórpido puedan estar desarrollando una OP

Organizing pneumonia in patients with severe respiratory failure due to novel A (H1N1) influenza.

The authors describe two cases that developed organizing pneumonia (OP) associated with novel influenza A(H1N1) virus. These patients were admitted to intensive care unit (ICU) because of severe respiratory failure. After initial clinical improvement, both patients worsened their condition during their second week of ICU stay, presenting fever, increasing in inflammatory parameters and worsening in oxygen exchange and respiratory mechanics. Chest x-rays and computed tomographies showed an increment on lung infiltrates, given by areas of consolidation and ground glass opacification. Although broad-spectrum antibiotics were administered, patients showed no improvement. All cultures, including bronchoalveolar lavage samples, were negative. In both cases, an open lung biopsy was performed, and histopathological examination of the specimen was compatible with OP. Both patients were successfully treated with high-dose corticoids. The aim of this report is to alert about the possibility of OP associated with novel influenza virus in patients with severe respiratory failure.

Influenza A (H1N1) organising pneumonia.

In November 2009, countries around the world reported confirmed cases of pandemic influenza H1N1, including over 6000 deaths. No peak in activity has been seen. The most common causes of death are pneumonia and acute respiratory distress syndrome. We report a case of a 55-year-old woman who presented with organising pneumonia associated with influenza A (H1N1) infection confirmed by transbronchial lung biopsy. Organising pneumonia should also be considered as a possible complication of influenza A (H1N1) infection, given that these patients can benefit from early diagnosis and appropriate specific management.

Differential role of the Fas/Fas ligand apoptotic pathway in inflammation and lung fibrosis associated with reovirus 1/L-induced bronchiolitis obliterans organizing pneumonia and acute respiratory distress syndrome.

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 x 10(6) (BOOP), or 1 x 10(7) (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-Fas(lpr-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.

Rapidly progressive organising pneumonia associated with cytomegalovirus infection in a patient with psoriasis.

A 63-year-old woman experienced progressive respiratory distress and psoriatic plaques. The radiographic images showed diffuse interstitial infiltrates. The surgical open lung biopsy revealed an obliteration of the alveolar spaces by plugs of connective tissue distributed within the terminal bronchioles, alveolar ducts and spaces. No relevant cause was determined, and she was diagnosed with idiopathic organising pneumonia. The patient was discharged with oral glucocorticosteroid and supplemental oxygen therapy. One month later, the patient's pulmonary status had progressively worsened, and she was re-admitted. She required higher oxygen concentrations and mechanical ventilation. Pharmacological therapy included high-dose steroids and cyclophosphamide. Serological assays revealed high antibodies titers (both IgM and IgG) to cytomegalovirus. Therefore, ganciclovir was added to the regimen. Despite the therapy, she died as a result of the disease. The review of the current literature on the topic is also presented.

Influenza A-associated bronchiolitis obliterans organizing pneumonia mimicking Wegener's granulomatosis.

We describe a patient with bronchiolitis obliterans organizing pneumonia (BOOP) requiring respiratory support and treated with corticosteroids and cytoxan for presumed Wegener's granulomatosis (WG). The diagnosis of WG was based on clinical presentation and strongly positive stains for anti-neutrophilic cytoplasmic antibodies (cANCA). The results of an open-lung biopsy were consistent with BOOP. Although BOOP has previously been described as one of the pulmonary manifestations of WG, other more specific histologic features of WG such as capillaritis or necrotizing vasculitis were lacking. Because influenza A virus was cultured from the patient's lung tissue, final assessment of the illness focused on this as the etiologic agent triggering the pulmonary syndrome. The presence of ANCA was considered to be nonspecific. The patient's condition improved with appropriate therapy for BOOP.

Respiratory reovirus 1/L induction of intraluminal fibrosis. A model for the study of bronchiolitis obliterans organizing pneumonia.

Bronchiolitis obliterans organizing pneumonia (BOOP) is a term that was first applied in 1985 to describe a long-observed but unclassified pattern of acute lung injury. BOOP lesions are characterized by fibrous extensions into the alveolar spaces in association with a peribronchiolar organizing pneumonia. Since 1985, an increasing number of reports of BOOP have appeared in the clinical literature, and it is now accepted that BOOP is a significant pulmonary syndrome. Although BOOP can be associated with a number of documented pulmonary insults, many cases are not associated with known causes and are thus classified as idiopathic. The lack of an appropriate small animal model that closely mimics the generation of BOOP lesions has been an impediment to basic studies of the pathogenic mechanisms responsible for the generation of BOOP in humans. In this report, we describe an animal model for BOOP in which CBA/J mice infected with reovirus serotype 1/strain Lang develop BOOP lesions. These lesions closely resemble those seen in humans and occur in a well defined temporal sequence that proceeds from initial peribronchiolar inflammatory lesions to characteristic, fibrotic cellular BOOP lesions over a 3-week time course.

A case of bronchiolitis obliterans organizing pneumonia associated with adenovirus.

A 58-year-old man described a short history of dyspnea and a preceding flu like illness with roentgenographic features of an interstitial lung disease. An open lung biopsy specimen from him showed bronchiolitis obliterans with organizing pneumonia (BOOP). Adenovirus was isolated from a throat swab. There was both clinical and radiographic improvement with supportive care. We herein report a first case of BOOP associated with adenovirus in Korea.

[Bronchiolitis obliterans with organized pneumonia associated with measles virus]. / Bronquiolitis obliterante con neumonía organizada relacionada con virus del sarampión.

Bronchiolitis obliterans with organizing pneumonia (BOOP) is a nonspecific form of pulmonary injury related to different etiologic agents. The disorder is not only limited to the alveoli but also affects to the alveolar ducts and distal bronchioles. This fact may differentiate this disorder of others with chronic inflammatory diffuse alveolar lesion as chronic eosinophilic pneumonia (CEP), extrinsic allergic alveolitis (EAA) or diffuse alveolar damage (DAD). It has been described an idiopathic form and other associated with connective tissue diseases, infections, organ's transplantation, drug or chemical induced reactions, irradiation pneumonitis and aspiration pneumonitis, among others. Their extremely variable clinical presentation and course, etiology, and histologic appearance and, in some way, the considerable confusion as a result to the different terminologies applied, has made difficult a clear understanding of this disease. We present two cases of BOOP related to infection by measles virus, whose diagnostic was obtained through pulmonary thoracoscopic biopsy and serological study respectively. Patients were treated with steroids (6 months) with a favorable outcome in terms of clinical symptoms, radiological findings, and a normalization of the pulmonary function tests. We suggest that in each patient with clinic and radiological study suspicious of BOOP, it seem to be useful to include measles virus in serologic study. This investigation may contribute to reduce the number of cases classified as idiopathic BOOP.