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.

A Case of Organizing Pneumonia Resembling Lung Cancer.

BACKGROUND: Organizing pneumonia (OP) is a pathologic diagnosis with clinical and imaging manifestations that often resemble other diseases, such as infections and cancers, which can lead to delays in diagnosis and inappropriate management of the underlying disease. In this article, we present a case of organized pneumonia that resembles lung cancer. METHODS: We report a case of initial suspicion of pulmonary malignancy, treated with anti-inflammatory medication and then reviewed with CT suggesting no improvement, and finally confirmed to be OP by pathological biopsy taken via transbronchoscopy. A joint literature analysis was performed to raise clinicians' awareness of the diagnosis and treatment of OP. RESULTS: Initially, because of the atypical auxiliary findings, we thought that the disease turned out to be a lung tumor, which was eventually confirmed as OP by pathological diagnosis. CONCLUSIONS: The diagnosis and treatment of OP requires a combination of clinical information and radiological expertise, as well as biopsy to obtain histopathological evidence. That is, clinical-imaging-pathological tripartite cooperation and comprehensive analysis.

Resolution of an insidious and migratory Mycobacterium tuberculosis-associated secondary organizing pneumonia: a case report and literature review.

BACKGROUND: Organizing pneumonia (OP) is a rare interstitial lung disease. Secondary organizing pneumonia (SOP) caused by Mycobacterium tuberculosis (MTB) is extremely rare. Migratory MTB-associated SOP is more deceptive and dangerous. When insidious tuberculosis (TB) is not recognized, SOP would be misdiagnosed as cryptogenic organizing pneumonia (COP). Use of steroid hormone alone leads to the progression of TB foci or even death. Clues of distinguishing atypical TB at the background of OP is urgently needed. CASE PRESENTATION: A 56-year-old female patient was hospitalized into the local hospital because of cough and expectoration for more than half a month. Her medical history and family history showed no relation to TB or other lung diseases. Community-acquired pneumonia was diagnosed and anti-infection therapy was initialized but invalid. The patient suffered from continuous weigh loss. More puzzling, the lesions were migratory based on the chest computed tomography (CT) images. The patient was then transferred to our hospital. The immunological indexes of infection in blood and pathogenic tests in sputum and the bronchoalveolar lavage fluid were negative. The percutaneous lung puncture biopsy and pathological observation confirmed OP, but without granulomatous lesions. Additionally, pathogen detection of the punctured lung tissues by metagenomics next generation sequencing test (mNGS) were all negative. COP was highly suspected. Fortunately, the targeted next-generation sequencing (tNGS) detected MTB in the punctured lung tissues and MTB-associated SOP was definitely diagnosed. The combined therapy of anti-TB and prednisone was administrated. After treatment for 10 days, the partial lesions were significantly resorbed and the patient was discharged. In the follow-up of half a year, the patient was healthy. CONCLUSIONS: It is difficult to distinguish SOP from COP in clinical practice. Diagnosis of COP must be very cautious. Transient small nodules and cavities in the early lung image are a clue to consider TB, even though all pathogen tests are negative. tNGS is also a powerful tool to detect pathogen, ensuring prompt diagnosis of TB-related SOP. For clinicians in TB high burden countries, we encourage them to keep TB in mind before making a final diagnosis of COP.

Properties of Pleural Mesothelial Cells in Idiopathic Pulmonary Fibrosis and Cryptogenic Organizing Pneumonia.

BACKGROUND: Profibrotic properties of pleural mesothelial cells may play an important role in the fibrosis activity in idiopathic pulmonary fibrosis (IPF). The purpose of this study was to compare the expression of pleural mesothelial cell markers in IPF and cryptogenic organizing pneumonia (COP), with an assumption that increased expression implies increase in fibrosis. METHODS: Twenty IPF lung samples were stained by immunohistochemistry for the pleural mesothelial cell markers: leucine rich repeat neuronal 4 (LRRN4), uroplakin 3B, CC-chemokine ligand 18, and laminin-5. Nine COP lung samples were used as controls. A semi-quantitative analysis was performed to compare markers expression in IPF and COP. RESULTS: LRRN4 expression was found in epithelial lining cells along the honeycombing and fibroblastic foci in IPF, but not in the fibrotic interstitial lesion and airspace filling fibrous tufts in COP. We found a significant decrease in baseline forced vital capacity when LRRN4 expression was increased in honeycombing epithelial cells and fibroblastic foci. CONCLUSION: LRRN4 expression patterns in IPF are distinct from those in COP. Our findings suggest that mesothelial cell profibrotic property may be an important player in IPF pathogenesis and may be a clue in the irreversibility of fibrosis in IPF.

Secondary organizing pneumonia after recovery of mild COVID-19 infection.

A 36-year-old male with diffuse large B-cell lymphoma on maintenance rituximab therapy presented to the emergency department with high fever and fatigue. A chest X-ray showed a lobar infiltrate, 40 days before admission the patient suffered from a mild coronavirus disease 2019 (COVID-19) infection and fully recovered. PCR nasopharyngeal swab was negative for COVID-19. Comprehensive biochemical, radiological, and pathological evaluation including 18-fluorodeoxyglucose positron emission tomography with computed tomography and transbronchial lung biopsy found no pathogen or lymphoma recurrence. Treatment for pneumonia with antibiotic and antifungal agents was nonbeneficial. A diagnosis of secondary organizing pneumonia (OP) was made after pneumonia migration and a rapid response to corticosteroids. OP secondary to a viral respiratory infection has been well described. Raising awareness for post-COVID-19 OP has therapeutic and prognostic importance because those patients benefit from steroid therapy. We believe the condition described here is underdiagnosed and undertreated by doctors worldwide. Because of the ongoing global pandemic we are now encountering a new kind of patient, patients that have recovered from COVID-19. We hope that this case may contribute to gaining more knowledge about this growing patient population.

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.

Comparison of clinical features and prognosis in patients with cryptogenic and secondary organizing pneumonia.

BACKGROUND: Organizing pneumonia (OP) can be diagnosed pathologically, and cryptogenic OP (COP) and secondary OP (SOP) have been classified by cause and particular underlying context. Because it is clinically difficult to differentiate between COP and SOP, this study investigated characteristics that could distinguish between COP and SOP. METHODS: The medical records of patients who underwent lung biopsy for a diagnosis of OP at a single tertiary hospital from January 2016 to December 2018 were retrospectively reviewed. RESULTS: Eighty-five patients had pathologically proven OP, including 16 diagnosed with COP and 69 diagnosed with SOP. The most common cause of SOP was infectious pneumonia, observed in 57 (82.6%) of the 69 patients, followed by cancer and radiation pneumonitis. The pathogens causing infectious pneumonia were identified in 45 (65.2%) patients. There were no differences in age, sex, and lung function between the COP and SOP groups. Median body mass index was significantly lower (P = 0.030), and median time from symptom onset to hospital admission significantly shorter (P = 0.006), in the SOP than in the COP group. Fever was more common in the SOP group (P = 0.024), and CURB 65, an index of pneumonia severity, tended to be higher in the SOP group (P = 0.017). Some laboratory results differed significantly between the two groups. Lymphocyte counts in bronchoalveolar lavage (BAL) fluid were significantly higher in the COP than in the SOP group (P = 0.012). Radiologic findings showed that effusion was more common in the SOP group (P = 0.036). There were no between-group differences in steroid use, 30 day and in-hospital mortality rates, and rates of OP outcomes and recurrences. Pneumonia recurrence rate was significantly higher in SOP patients who were than were not treated with steroids (P = 0.035). CONCLUSIONS: Infection is the main cause of SOP. Symptom onset is more rapid in patients with SOP than with COP. Some blood and BAL fluid test results differed significantly in the COP and SOP groups. Pleural effusion was more common in the SOP group but there were no differences in clinical course. Recurrence in patients with SOP was more common in those who were than were not treated with steroids.

[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.

Pulmonary tuberculosis presenting secondary organizing pneumonia with organized polypoid granulation tissue: case series and review of the literature.

BACKGROUND: Secondary organizing pneumonia (SOP) is difficult to distinguish from cryptogenic organizing pneumonia (COP) considering various clinical situations. SOP caused by Mycobacterium tuberculosis is rare; indeed, it has not been reported as a sequela of disseminated tuberculosis. METHODS: From January 2016 to December 2018, we identified six cases of tuberculosis-associated SOP in which Mycobacterium tuberculosis was revealed by microbiological examination; one of the cases was miliary tuberculosis. RESULTS: Of the six cases, 17% were positive for acid fast bacillus (AFB) stain, but 100% were positive for M. tuberculosis polymerase chain reaction (MTB PCR) and AFB culture. In all cases, transbronchial lung biopsy was performed and organizing pneumonia was confirmed pathologically. All survived after treatment with anti-tuberculosis therapy. CONCLUSIONS: Pulmonary tuberculosis, which shows OP in lung biopsy, is diagnosed through MTB PCR and AFB culture, and the prognosis is thought to be good.

Gross and Histopathological Findings in the First Reported Vaping-Induced Lung Injury Death in the United States.

The popularity of e-cigarettes (vaping) has been on the rise in recent years, but the adverse effects of vaping have been greatly unknown. In 2019, the use of vaping products has been linked to an outbreak of severe lung disease, some cases of which have progressed to death. One death attributed to vaping is presented with emphasis on the gross and histopathological findings from the autopsy. These findings were correlated with the patient's clinical course and medicolegal investigation to determine the cause of death. To our knowledge, this is the first confirmed death in the United States that was directly attributed to the use of vaping.

[Analysis of clinical characteristics of 21 cases of acute fibrinous and organizing pneumonia].

Objective: To summarize the clinical features of 21 cases of acute fibrinous and organizing pneumonia (AFOP) confirmed by pathology, thereby improving clinicians' understanding of this disease and avoiding misdiagnosis in clinical practice. Methods: Twenty-one patients diagnosed pathologically with AFOP from January 2016 to April 2019 were analyzed retrospectively. The clinical symptoms, laboratory examination results, imaging features, treatments and outcomes were analyzed comprehensively. Results: There were 10 males and 11 females, with an average age of (58±10) years. All the cases presented subacute disease onset. The main symptoms were cough, expectoration and fever. The results from laboratory examination showed that the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were significantly higher than the normal levels. The total number of leukocytes, the percentage of neutrophils, and procalcitonin were also higher than the normal levels. Among these patients, 4 cases showed positive sputum bacteriology. Nine patients were found to have probable etiological factors (infections in 4, tumors in 4 cases, and connective tissue disease in 1 case). Twelve patients had no confirmed etiological factors. As to radiological findings, the patterns were multiple patchy infiltrates(16/21), solitary mass (3/21) and multiple nodules in both lungs (2/21). Most lesions were subpleural in distribution (15/21), with air bronchogram sign (11/21), pleural effusion (9/21), and cavity (4/21). Three patients received anti-infective therapy only. The infiltration in lung disappeared within 2 months in one patient, but the lesion still existed in one case after three years of follow-up. However, one patient were lost during the follow-up. Eighteen patients were treated with oral glucocorticoids, and about 50% of the patients showed significant improvement in symptoms and imaging findings within one month. The average follow-up time was (22±10) months, and there was no death. Conclusions: The clinical and imaging findings of AFOP are nonspecific. The exact mechanism of its pathogenesis is not clear. Infection and tumor may be related to the pathogenesis of AFOP. AFOP with subacute onset has a good response to glucocorticoid treatment with a better prognosis.

Utility of procalcitonin for differentiating cryptogenic organising pneumonia from community-acquired pneumonia.

Background This study aimed to investigate the usefulness of inflammatory biomarkers such as white blood cell (WBC) count, C-reactive protein (CRP) and procalcitonin (PCT) for differentiating cryptogenic organising pneumonia (COP) from community-acquired pneumonia (CAP). Methods COP patients hospitalised in Kurashiki Central Hospital between January 2010 and December 2017 whose WBC counts and CRP and PCT levels were measured were investigated retrospectively, and their results were compared with those of hospitalised CAP patients who were prospectively enrolled between October 2010 and November 2017. Definite COP was defined by specific histopathological findings, and possible COP was defined as a consolidation shadow on chest computed tomography and lymphocyte dominance in bronchoalveolar lavage fluid in the absence of specific histopathological findings or lung specimens. The discriminatory abilities of WBC counts, CRP and PCT were evaluated by receiver operating characteristic (ROC) curve analysis. Results There were 56 patients in the entire COP group, 35 (61.4%) with definite COP, and 914 CAP patients. All three biomarkers were significantly lower in COP than in CAP. The AUC value of PCT in all COP patients was 0.79, significantly higher than of both CRP (AUC 0.59, p < 0.001) and WBC (AUC 0.69, p = 0.048). In definite COP patients, the AUC value of PCT was 0.79, which was also significantly higher than of both WBC (AUC 0.64, p = 0.006) and CRP (AUC 0.64, p = 0.001). Conclusions PCT is a more useful biomarker for differentiating COP from CAP than WBC count or CRP. However, PCT should be used as an adjunct to clinical presentation and radiological findings.

Acute fibrinous and organizing pneumonia: two case reports and literature review.

BACKGROUND: Acute fibrinous and organizing pneumonia (AFOP) is a very rare form of acute or subacute lung injury, which is characterized by patches of "fibrin balls" distributed within the alveoli. Given the lack of typical clinical manifestations, AFOP is often misdiagnosed as pneumonia, tuberculosis, etc. Definitive diagnosis is obtained from a lung biopsy. Corticosteroids are usually effective. CASE PRESENTATION: We report two cases of patients with histopathological manifestations of AFOP, which were significantly improved after corticosteroid therapy. Previous reports of the clinical and pathological characteristics of AFOP were reviewed to improve clinicians' understanding of this disease. CONCLUSIONS: Early identification and diagnosis are very important for AFOP treatment. The prognosis is acceptable after timely and effective treatment.

Predictive factors for relapse of cryptogenic organizing pneumonia.

BACKGROUND: Relapse of cryptogenic organizing pneumonia (COP) may lead to poor long-term prognosis and necessitates multiple rounds of steroid treatment with potential adverse effects. The objective of this study is to identify predictive factors of COP relapse by comparing demographic and clinical variables between relapse and non-relapse groups. METHODS: During 2008-2013, 33 COP patients were treated, of which 23 (69.7%) and 10 patients (30.3%) were assigned to the non-relapse and relapse group, respectively. From medical records, we compared the following variables at initial episode: clinical characteristics, serum parameters, chest CT scan findings, and steroid treatment. RESULTS: Clinical characteristics, cumulative prednisone dose, and steroid treatment duration were similar between groups. In univariate analysis, alternatively, the proportion of patients with bilateral shadow pattern, traction bronchiectasis, and partial remission after steroid treatment was significantly higher in the relapse group. These differences were not significant by multivariate Cox regression analysis. CONCLUSIONS: We identified radiographic findings, such as bilateral shadow pattern, traction bronchiectasis, and partial remission, may have possibility of predictive factors for COP relapse. Larger-scale studies are required to confirm if any are independent predictors of COP relapse.

Secondary organizing pneumonia (bronchiolitis obliterans with organizing pneumonia) associated with adalimumab for treatment of chronic plaque psoriasis.

Organizing pneumonia is defined histopathologically by intra-alveolar buds of granulation tissue, consisting of intermixed myofibroblasts and connective tissue. The pathological pattern of organizing pneumonia may be idiopathic or related to a determined cause, termed secondary organizing pneumonia. We report a 68-year-old woman with a longstanding history of chronic plaque psoriasis, treated with the tumor necrosis factor (TNF) inhibitor, adalimumab. After 8 years of treatment, she developed a gradual-onset, non-productive cough with associated generalized fatigue and mild dyspnea. Radiological investigations demonstrated ground-glass opacities in the left lower lobe and bronchoscopy revealed a fibroinflammatory process consistent with organizing pneumonia. Her biologic treatment was ceased and corticosteroid treatment commenced, with resolution of both her symptoms and the radiological findings. Given the increasing incidence of biologic treatment in the management of dermatological conditions, clinicians should be aware of secondary organizing pneumonia as a possible side effect of TNF inhibitor therapy.

Cicatricial organising pneumonia mimicking a fibrosing interstitial pneumonia.

AIMS: Organising pneumonia (OP) is composed of loose granulation tissue plugs in distal airspaces; these disappear with steroid treatment. Recently a variant labelled 'cicatricial' OP has been described in which the granulation tissue organised to much denser fibrous tissue but still retained the usual pattern of OP. Here we report 10 patients thought to have an interstitial lung disease, and who on biopsy had a variant of cicatricial OP characterised by linear bands or small nodular masses of dense fibrous tissue that does not resemble ordinary OP. METHODS AND RESULTS: The bands/nodules were usually distributed randomly but occasionally resembled fibrotic non-specific interstitial pneumonia in local areas. Small foci of loose granulation tissue at the edge of the fibrotic bands sometimes mimicked fibroblast foci. Recognisable conventional OP was always present, but often in very small amounts. Four cases, including one patient with Ehlers-Danlos syndrome, showed formation of bone in the fibrotic bands and nodules. On computerised tomography (CT) scan of the chest some cases looked like typical OP, but some demonstrated only irregularly distributed linear opacities, sometimes with associated calcification. Follow-up imaging on six cases showed that the process either markedly improved or remained stable over time; no case had progressive disease. CONCLUSIONS: Cicatricial OP with this pathological pattern represents an uncommon form of OP that appears to be a generally benign process which may have persisting linear opacities on CT scan but that does not progress; however, it can be confused on biopsy and CT with a fibrosing interstitial pneumonia.

Serial chest CT in cryptogenic organizing pneumonia: Evolutional changes and prognostic determinants.

BACKGROUND AND OBJECTIVE: Cryptogenic organizing pneumonia (COP) is corticosteroid responsive but residual computed tomography (CT) chest changes are often noted. The present study examined clinical and HRCT features of COP in which there was incomplete resolution. METHODS: We studied 93 patients with histopathologically confirmed COP and serial HRCT imaging. Clinical features were assessed, and serial CT images were analysed. Uni- and multivariate analyses were performed to determine clinical or imaging factors related to incomplete resolution on CT. RESULTS: Complete resolution on CT imaging was seen in 21/93 patients (23%) and residual abnormalities were seen in 72/93 patients (77%). In univariate analysis, total lesion (P = 0.036), degree of consolidation (P = 0.011), treatment duration (P < 0.001) and single-breath carbon monoxide diffusing capacity of lung (P = 0.021) were significantly associated with residual imaging abnormalities. In multivariate analysis, extent of consolidation (P = 0.018; odds ratio (OR) = 14.92) and treatment duration (P = 0.011; OR = 1.32) remained as significant factors linked to residual abnormalities. CT images in unresolved COP were akin to fibrotic non-specific interstitial pneumonia (fNSIP) in 53/72 (74%) patients. CONCLUSION: Clinical, radiological and lung diffusion measurements were related to incomplete resolution on CT after COP. Imaging abnormalities on CT chest generally resembled fNSIP.