Novel Patterns in High-Resolution Computed Tomography in Whipple Pneumonia.

With the use of metagenomic next-generation sequencing, patients diagnosed with Whipple pneumonia are being increasingly correctly diagnosed. We report a series of 3 cases in China that showed a novel pattern of movable infiltrates and upper lung micronodules. After treatment, the 3 patients recovered, and lung infiltrates resolved.

Gut-derived fungemia due to Kodamaea ohmeri combined with invasive pulmonary aspergillosis: a case report.

BACKGROUND: Kodamaea ohmeri is a rare pathogen with high mortality and is found among blood samples in a considerable proportion; however, gastrointestinal infection of K. ohmeri is extremely rare. Invasive pulmonary aspergillosis is also an uncommon fungal; these two fungal infections reported concomitantly are unprecedented. CASE PRESENTATION: We described a case of a 37-year-old male who got infected with K. ohmeri and invasive pulmonary aspergillosis. We used the mass spectrometry and histopathology to identify these two fungal infections separately. For the treatment of K. ohmeri, we chose caspofungin. As for invasive pulmonary aspergillosis, we used voriconazole, amphotericin B, and then surgery. The patient was treated successfully through the collaboration of multiple disciplines. CONCLUSIONS: We speculate that the destruction of the intestinal mucosa barrier can make the intestine one of the ways for certain fungi to infect the human body.

Inhibition of macrophage migration inhibitory factor (MIF) as a therapeutic target in bleomycin-induced pulmonary fibrosis rats.

Macrophage migration inhibitory factor (MIF) inhibition can attenuate pulmonary fibrosis, but the antifibrotic mechanism is unclear. Here we investigated the antifibrotic effect of MIF knockdown in rats with bleomycin (BLM)-induced pulmonary fibrosis. The results showed that MIF inhibition attenuated lung injury and extracellular matrix deposition; significantly reduced the levels of cytokines including transforming growth factor-ß1 (TGF-ß1), tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), hydroxyproline (hyp), fibroblast growth factor 23 (FGF23), and secreted phosphoprotein 1 (Spp1); and inhibited the expression of CD68, F4/80, and α-smooth muscle actin (α-SMA) protein. MIF inhibition is associated with reduction of proinflammatory mediators and macrophage infiltration in lungs. In addition, MIF knockdown in the day 14 group was significantly better than MIF knockdown in day 1 group in terms of the above mentioned cytokines TGF-ß1, IL-17, TNF-α. MIF knockdown in day 14 group showed a better trend than MIF knockdown in day 1 group in inhibition of hyp and α-SMA formation. Furthermore, MIF inhibition downregulated the FGF23, Spp1, anti-integrin alpha 10 (Itga10), laminin subunit alpha 1 (Lama1), thrombospondin 2 (THBS2), and Serpin family B member 5 (SERPINB5) mRNA levels and the p-Smad2/3 protein level. MIF knockdown may inhibit fibrosis through the TGF-ß1/Smads signaling pathway. In addition, MIF inhibition protects against vascular remodeling via Thbs2 and Serpinb5 signaling. In summary, our study showed that knockdown of MIF can significantly inhibit lung inflammation and fibrosis in rats with BLM-induced pulmonary fibrosis. The future development of inhibitors targeting MIF may contribute to the treatment of pulmonary fibrosis.

Dynamic changes in lymphocyte subsets and parallel cytokine levels in patients with severe and critical COVID-19.

BACKGROUND: The lack of knowledge regarding the pathogenesis and host immune response during SARS-CoV-2 infection has limited the development of effective treatments. Thus, we longitudinally investigated the dynamic changes in peripheral blood lymphocyte subsets and parallel changes in cytokine levels in COVID-19 patients with different disease severities to further address disease pathogenesis. METHODS: A total of 67 patients (10 moderate, 38 severe and 19 critical cases) with COVID-19 admitted to a tertiary care hospital in Wuhan from February 8th to April 6th, 2020 were retrospectively studied. Dynamic data of lymphocyte subsets and inflammatory cytokines were collected. RESULTS: On admission, compared with moderate cases, severe and critical cases showed significantly decreased levels of total lymphocytes, T lymphocytes, CD4+ T cells, CD8+ T cells, B cells and NK cells. IL-6 and IL-10 were significantly higher in the critical group. During the following hospitalization period, most of the lymphocyte subsets in the critical group began to recover to levels comparable to those in the severe group from the fourth week after illness onset, except for NK cells, which recovered after the sixth week. A sustained decrease in the lymphocyte subsets and an increase in IL-6 and IL-10 were observed in the nonsurvivors until death. There was a strong negative correlation between IL-6 and IL-10 and total lymphocytes, T lymphocytes, CD4+ T cells, CD8+ T cells and NK cells. CONCLUSIONS: A sustained decrease in lymphocyte subsets, especially CD4+ T cells and NK cells, interacting with proinflammatory cytokine storms was associated with severe disease and poor prognosis in COVID-19.

Tiotropium in Early-Stage Chronic Obstructive Pulmonary Disease.

BACKGROUND: Patients with mild or moderate chronic obstructive pulmonary disease (COPD) rarely receive medications, because they have few symptoms. We hypothesized that long-term use of tiotropium would improve lung function and ameliorate the decline in lung function in patients with mild or moderate COPD. METHODS: In a multicenter, randomized, double-blind, placebo-controlled trial that was conducted in China, we randomly assigned 841 patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1 (mild) or 2 (moderate) severity to receive a once-daily inhaled dose (18 µg) of tiotropium (419 patients) or matching placebo (422) for 2 years. The primary end point was the between-group difference in the change from baseline to 24 months in the forced expiratory volume in 1 second (FEV1) before bronchodilator use. Secondary end points included the between-group difference in the change from baseline to 24 months in the FEV1 after bronchodilator use and the between-group difference in the annual decline in the FEV1 before and after bronchodilator use from day 30 to month 24. RESULTS: Of 841 patients who underwent randomization, 388 patients in the tiotropium group and 383 in the placebo group were included in the full analysis set. The FEV1 in patients who received tiotropium was higher than in those who received placebo throughout the trial (ranges of mean differences, 127 to 169 ml before bronchodilator use and 71 to 133 ml after bronchodilator use; P<0.001 for all comparisons). There was no significant amelioration of the mean (±SE) annual decline in the FEV1 before bronchodilator use: the decline was 38±6 ml per year in the tiotropium group and 53±6 ml per year in the placebo group (difference, 15 ml per year; 95% confidence interval [CI], -1 to 31; P=0.06). In contrast, the annual decline in the FEV1 after bronchodilator use was significantly less in the tiotropium group than in the placebo group (29±5 ml per year vs. 51±6 ml per year; difference, 22 ml per year [95% CI, 6 to 37]; P=0.006). The incidence of adverse events was generally similar in the two groups. CONCLUSIONS: Tiotropium resulted in a higher FEV1 than placebo at 24 months and ameliorated the annual decline in the FEV1 after bronchodilator use in patients with COPD of GOLD stage 1 or 2. (Funded by Boehringer Ingelheim and others; Tie-COPD ClinicalTrials.gov number, NCT01455129 .).

Efficacy and tolerability of budesonide/formoterol added to tiotropium compared with tiotropium alone in patients with severe or very severe COPD: A randomized, multicentre study in East Asia.

BACKGROUND AND OBJECTIVE: Triple combination therapy with tiotropium plus budesonide/formoterol has improved lung function and reduced exacerbation risk in patients with chronic obstructive pulmonary disease (COPD) in Western countries, but no such data exist for East Asian patients. This study aimed to evaluate the efficacy and tolerability of adding budesonide/formoterol to tiotropium compared with tiotropium alone in East Asian patients with severe/very severe COPD. METHODS: This 12-week, randomized, parallel-group, multicentre, open-label study was conducted in East Asia. After a 14-day run-in period during which patients received tiotropium 18 µg once daily, patients were randomized to tiotropium (18 µg once daily) + budesonide/formoterol (160/4.5 µg 2 inhalations twice daily) or tiotropium alone (18 µg once daily). The primary endpoint was change from baseline in pre-dose forced expiratory volume in 1 s (FEV1 ) to the mean of values measured at Weeks 1, 6 and 12. RESULTS: Pre-dose FEV1 significantly increased from baseline with tiotropium plus budesonide/formoterol (n = 287) versus tiotropium alone (n = 291) (5.0% vs 0.6%; treatment difference: 4.4% (95% CI: 1.9-6.9), P = 0.0004). Triple therapy also reduced the COPD exacerbation rate by 40.7% (P = 0.0032) and prolonged time to first exacerbation (38.6% risk reduction, P = 0.0167) versus tiotropium alone and markedly improved health-related quality of life (HRQoL), measured using the St George's Respiratory Questionnaire. Incidence of adverse events was 26% for both groups. CONCLUSIONS: In East Asian patients with severe/very severe COPD, adding budesonide/formoterol to tiotropium was associated with significant improvements in FEV1 and HRQoL and lower COPD exacerbation rates. Treatment was generally well tolerated. CLINICAL TRIAL REGISTRATION: NCT01397890 at Clinicaltrials.gov.

Meta-analysis of the adverse effects of long-term azithromycin use in patients with chronic lung diseases.

The adverse effects of azithromycin on the treatment of patients with chronic lung diseases (CLD) were evaluated in the present study. MEDLINE and other databases were searched for relevant articles published until August 2013. Randomized controlled trials that enrolled patients with chronic lung diseases who received long-term azithromycin treatment were selected, and data on microbiological studies and azithromycin-related adverse events were abstracted from articles and analyzed. Six studies were included in the meta-analysis. The risk of bacterial resistance in patients receiving long-term azithromycin treatment was increased 2.7-fold (risk ratio [RR], 2.69 [95% confidence interval {95% CI}, 1.249, 5.211]) compared with the risk in patients receiving placebo treatment. On the other hand, the risk of bacterial colonization decreased in patients receiving azithromycin treatment (RR, 0.551 [95% CI, 0.460, 0.658]). Patients receiving long-term azithromycin therapy were at risk of increased impairment of hearing (RR, 1.168 [95% CI, 1.030, 1.325]). This analysis provides evidence supporting the idea that bacterial resistance can develop with long-term azithromycin treatment. Besides the increasingly recognized anti-inflammatory role of azithromycin used in treating chronic lung diseases, we should be aware of the potential for adverse events with its long-term use.

Down-regulation of Aquaporin1 (AQP1) by peptidoglycan via p38 MAPK pathways in primary rat pleural mesothelial cells.

BACKGROUND AND OBJECTIVE: This study was designed to investigate the p38 mitogen-activated protein kinase (MAPK) signaling pathway involved in Aquaporin1 (AQP1) expression caused by staphylococcal peptidoglycan (PGN) in cultured rat pleural mesothelial cells (rPMCs) in vitro. METHODS: RT-PCR and immunoblot analysis were used to determine the relative mRNA and protein levels of AQP1 by PGN in rPMCs. P38 kinase inhibitor SB203580, JNK inhibitor SP600125, and ERK1/2 inhibitor PD98059 were used to determine the effects of PGN-induced AQP1 expression by immunoblot. Activation of p38 by PGN was reflected by detecting the phosphorylation constituent of p38, using immunoblot. The shift of localization after activation of p38 by PGN was investigated by immunofluorescence assay. RESULTS: AQP1 transcription and protein expression were decreased by PGN in dose-dependent and time-dependent manners in rPMCs. Down-regulation of AQP1 by PGN was blocked only by SB203580, neither by SP600125 nor by PD98059. Furthermore, rPMCs exposed to PGN showed activation of p38 MAPK. Phospho-p38 protein production was increased by PGN stimulation in rPMCs. The localization of phospho-p38 was both in the cytosol and nuclei after PGN treatment, while its normal distribution is mainly in the cytosol in rPMCs. CONCLUSION: AQP1 expression was decreased by PGN in both dose-dependent and time-dependent manners in rPMCs. This down-regulation by PGN-induced AQP1 in rPMCs may be mediated by the activation of p38 MARK pathway.

Decreased CD34+ cell number is correlated with cardiac dysfunction in patients with acute exacerbation of COPD.

BACKGROUND AND PURPOSE: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is associated with a higher risk of cardiovascular disease (CVD). Previous studies have indicated that the reduction of bone marrow-derived multipotent progenitors (CD34+ cells) may lead to reduced vascular repair capacity and may help to identify patients that pose an increased cardiovascular risk. However, the relationship between CD34+cells and CVD risk in AECOPD remains unclear. The aim of the present study was to assess CD34+ cell counts and their relationship with classical adverse cardiac outcome predictors in AECOPD. METHODS: For our study, 27 patients with AECOPD (GOLD stage III, IV), 26 with stable COPD (GOLD stage III, IV), and 24 healthy controls were enrolled. CD34+ cells were enumerated, and plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), a systemic inflammation marker (high-sensitivity C-reactive protein, hsCRP) and mobilisation marker (matrix metalloproteinase-9, MMP-9), were measured. Echocardiography was performed to evaluate cardiac dysfunction and pulmonary hypertension. RESULTS: Compared with healthy controls, AECOPD patients had a significantly decreased CD34+ cell count (5.1 ± 2.6 versus 9.4 ± 3.6 × 10³/ml), especially in patients with a prior history of acute exacerbation. For patients with AECOPD, the CD34+ cell count was inversely correlated with NT-proBNP levels, pulmonary artery systolic pressure (PASP) and resting heart rate, and positively correlated with left ventricular ejection fraction (LVEF). In all three groups, CD34+ cell count was negatively correlated with hsCRP. CONCLUSIONS: The circulating CD34+ cell count was decreased and correlated with cardiac dysfunction in AECOPD patients, and thus may account for the increased cardiovascular risk in this population.

NF-κB inhibition after cecal ligation and puncture reduces sepsis-associated lung injury without altering bacterial host defense.

INTRODUCTION: Since the NF-κB pathway regulates both inflammation and host defense, it is uncertain whether interventions targeting NF-κB would be beneficial in sepsis. Based on the kinetics of the innate immune response, we postulated that selective NF-κB inhibition during a defined time period after the onset of sepsis would reduce acute lung injury without compromising bacterial host defense. METHODS: Mice underwent cecal ligation and puncture (CLP). An NF-κB inhibitor, BMS-345541 (50 µg/g mice), was administered by peroral gavage beginning 2 hours after CLP and repeated at 6 hour intervals for 2 additional doses. RESULTS: Mice treated with BMS-345541 after CLP showed reduced neutrophilic alveolitis and lower levels of KC in bronchoalveolar lavage fluid compared to mice treated with CLP+vehicle. In addition, mice treated with CLP+BMS had minimal histological evidence of lung injury and normal wet-dry ratios, indicating protection from acute lung injury. Treatment with the NF-κB inhibitor did not affect the ability of cultured macrophages to phagocytose bacteria and did not alter bacterial colony counts in blood, lung tissue, or peritoneal fluid at 24 hours after CLP. While BMS-345541 treatment did not alter mortality after CLP, our results showed a trend towards improved survival. CONCLUSION: Transiently blocking NF-κB activity after the onset of CLP-induced sepsis can effectively reduce acute lung injury in mice without compromising bacterial host defense or survival after CLP.

Structure and function of OprD protein in Pseudomonas aeruginosa: from antibiotic resistance to novel therapies.

Pseudomonas aeruginosa (P. aeruginosa) is a common pathogen isolated from patients with nosocomial infections. Due to its intrinsic and acquired antimicrobial resistance, limited classes of antibiotics can be used for the treatment of infection with P. aeruginosa. Of these, the carbapenems are very important; however, the occurrence of carbapenem-resistant strains is gradually increasing over time. Deficiency of the outer membrane protein OprD confers P. aeruginosa a basal level of resistance to carbapenems, especially to imipenem. Functional studies have revealed that loops 2 and 3 in the OprD protein contain the entrance and/or binding sites for imipenem. Therefore, any mutation in loop 2 and/or loop 3 that causes conformational changes could result in carbapenem resistance. OprD is also a common channel for some amino acids and peptides, and competition with carbapenems through the channel may also occur. Furthermore, OprD is a highly regulated protein at transcriptional and post-transcriptional levels by some metals, small bioactive molecules, amino acids, and efflux pump regulators. Because of its hypermutability and highly regulated properties, OprD is thought to be the most prevalent mechanism for carbapenem resistance in P. aeruginosa. Developing new strategies to combat infection with carbapenem-resistant P. aeruginosa lacking OprD is an ongoing challenge.

Human endothelial progenitor cells isolated from COPD patients are dysfunctional.

Cardiovascular disease is the leading cause of morbidity and mortality in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). More than 44% of these patients present with generalized atherosclerosis at autopsy. It is accepted that endothelial progenitor cells (EPCs) participate in the repair of dysfunctional endothelium and thus protects against atherosclerosis. However, whether COPD affects the repairing capacity of EPCs is unknown. Therefore, the objective of this study was to determine whether and how EPCs are involved in the vascular repair process in patients with COPD. In our study, EPCs from 25 COPD and 16 control patients were isolated by Ficoll density-gradient centrifugation and identified using fluorescence activated cell sorting. Transwell Migratory Assay was performed to determine the number of EPC colony-forming units and the adherent capacity late-EPCs to human umbilical vein endothelial cells. Following arterial damage in NOD/SCID mice, the number of EPCs incorporated at the injured vascular site was determined using a fluorescence microscope. We found that the number of EPC clusters and cell migration, as well as the expression of CXCR4, was significantly decreased in patients with COPD. Additionally, the number of late-EPCs adherent to HUVEC tubules was significantly reduced, and fewer VEGFR2(+)-staining cells were incorporated into the injured site in COPD patients. Our study demonstrates that EPC capacity of repair was affected in COPD patients, which may contribute to altered vascular endothelium in this patient population.

Association of increased basic salivary proline-rich protein 1 levels in induced sputum with type 2-high asthma.

BACKGROUND: The aim of this study is to reveal whether basic salivary proline-rich protein BstNI subfamily 1 (PRB1) may be used as a diagnostic biomarker for type 2-high asthma. METHODS: PRB1 protein levels in the induced sputum of 67 subjects with asthma and 27 controls were determined by an enzyme-linked immunosorbent assay. Correlation analyses between PRB1 in the induced sputum and airway inflammatory indicators were also performed. RESULTS: PRB1 protein levels were significantly upregulated in the induced sputum of asthmatic patients (p =0.0098) and correlated with clinical eosinophil-related indicators and type 2 airway inflammation. These results indicate that PRB1 is a promising biomarker for type 2-high asthma. CONCLUSIONS: The expression of PRB1 in induced sputum is a potential biomarker for type 2-high asthma. The results of this study present new insights into the diagnosis and treatment of asthma.

Intermittent hypoxia-induced METTL3 downregulation facilitates MGLL-mediated lipolysis of adipocytes in OSAS.

Intermittent hypoxia (IH) is the core pathological feature of obstructive sleep apnea syndrome (OSAS), and insulin resistance (IR) is the most common metabolic complication of OSAS. Studies have shown that the levels of free fatty acids (FFAs), which are mainly released from adipocytes by lipolysis, are elevated in OSAS and play an important role in the development of IR. However, whether and how IH regulates adipocyte lipolysis in OSAS is not clear. Here, we revealed that the apnea hypopnea index was positively correlated with the serum levels of FFAs and FFA release from adipocytes in OSAS. In addition, IH facilitated lipolysis and FFA release from adipocytes by downregulating the level of METTL3. METTL3 downregulation impaired N6-methyladenosine (m6A) levels in MGLL mRNA and reduced MGLL expression, thereby promoting lipolysis. In addition, we identified YTHDF2 as the m6A reader that interacts with MGLL mRNA, accelerating its degradation. Furthermore, our data showed reduced levels of METTL3 and elevated levels of MGLL in the adipose tissues of OSAS patients and indicated an effect of METTL3 on lowering FFA levels and improving IR in rats with chronic IH. In conclusion, our study provides new insights into the development and treatment of IR in OSAS.

PTPRH Alleviates Airway Obstruction and Th2 Inflammation in Asthma as a Protective Factor.

PURPOSE: PTPRH inhibits EGFR activity directly in cancer patients and activated EGFR induces goblet cell hyperplasia and mucus hypersecretion in asthma. However, the function of PTPRH in asthma remains unknown. The purpose of this study was to access the association of PTPRH with asthma and its underlying mechanism. PATIENTS AND METHODS: We examined the PTPRH level in asthma patients (n = 108) and healthy controls (n = 35), and analyzed the correlations between PTPRH and asthma-related indicators. Human bronchial epithelial cell (HBECs) transfected with PTPRH and asthma mouse model were set up to investigate the function of PTPRH. RESULTS: The expression of PTPRH was significantly increased and correlated with pulmonary function parameters, including airway obstruction, and T-helper2 (Th2) associated markers in asthma patients. PTPRH increased in the house dust mite (HDM)-induced asthmatic mice, while Th2 airway inflammation and Muc5ac suppressed when treated with PTPRH. Accordingly, PTPRH expression was markedly increased in IL-13-stimulated HBECs but PTPRH over-expression suppressed MUC5AC. Moreover, HBECs transfected with over-expressed PTPRH inhibited the phosphorylation of EGFR, ERK1/2 and AKT, while induced against PTPRH in HBECs dephosphorylated of EGFR, ERK1/2 and AKT. CONCLUSION: PTPRH reduces MUC5AC secretion to alleviate airway obstruction in asthma via potential phosphorylating of EGFR/ERK1/2/AKT signaling pathway, which may provide possible therapeutic implications for asthma.

Meta-analysis and systematic review of procalcitonin-guided therapy in respiratory tract infections.

Circulating procalcitonin (PCT) is a biomarker that can be used in diagnosing bacterial infections. We performed a quantitative meta-analysis of available randomized controlled trials to determine whether antibiotic therapy based on PCT measurements alters clinical outcomes and antibiotic use in patients with lower respiratory tract infections. We identified studies through MEDLINE (1996 to 2010), the ISI Web of Knowledge (1996 to 2010), and Ovid. Studies that met our criteria were prospective, randomized controlled trials involving patients with respiratory tract infections. Outcomes of mortality, intensive care unit (ICU) admission, length of hospital stay, number of antibiotic prescriptions, and duration of antibiotic treatment were evaluated. Eight studies randomizing 3,431 patients met our criteria for inclusion. Pooled analysis showed a significant reduction in number of antibiotic prescriptions and duration of antibiotic use in patients with PCT-guided antibiotic treatment compared to standard therapy. In addition, the use of PCT-guided antibiotic therapy did not impact mortality, ICU admission, or length of hospital stay in these studies. A high degree of heterogeneity was identified in 3 of 5 outcomes that were evaluated, and sensitivity analysis indicated that heterogeneity was decreased among studies using the same PCT-based treatment algorithm. In conclusion, PCT-guided antibiotic therapy in patients with respiratory tract infections appears to reduce antibiotic use without affecting overall mortality or length of stay in the hospital.

Effects of downregulation of aquaporin1 by peptidoglycan and lipopolysaccharide via MAPK pathways in MeT-5A cells.

This study was designed to investigate the signaling pathway involved in aquaporin1 (AQP1) expression caused by peptidoglycan (PGN) from Staphylococcus aureus and lipopolysaccharide (LPS) in human pleural mesothelial cell lines (MeT-5A) in vitro. RT-PCR, immunoblot analysis, and immunofluorescence assay were used to determine the relative mRNA and protein levels of AQP1 caused by PGN and LPS in MeT-5A cells. Activation of MAPKs by PGN and LPS was reflected by detecting the phosphorylation constituents of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 using immunoblot. MAPKs inhibitors were used to determine the effects of PGN- and LPS-induced AQP1 expression by immunoblot. AQP1 transcription and protein expression were decreased by PGN and LPS in dose- and time-dependent manners in MeT-5A cells. Both PGN and LPS activated p38/ERK/JNK pathways in MeT-5A cells. Furthermore, downregulation of AQP1 expression by LPS was blocked by SB203580, SP600125, and PD98059, which are inhibitors of p38, JNK, and ERK1/2, respectively. In contrast, downregulation of AQP1 expression by PGN was blocked only by SB203580, not by SP600125 or PD98059, underlying the importance of p38 MAPK in the downregulation of AQP1 expression by PGN in MeT-5A cells. AQP1 expression was decreased by both PGN and LPS in dose- and time-dependent manners in MeT-5A cells. AQP1 expression was down-regulated by PGN via p38 MAPK pathway, while AQP1 expression was down-regulated by LPS via p38/JNK/ERK pathways.

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

BACKGROUND: Acute fibrinous and organizing pneumonia (AFOP) is a rare histologic interstitial pneumonia pattern characterized by the intra-alveolar fibrin deposition and organizing pneumonia. Its clinical characteristics are still not well known and there is no consensus on treatment yet. CASE PRESENTATION: We report two female cases in their fifties diagnosed with AFOP confirmed by a second lung biopsy. Case 1 was idiopathic AFOP with manifestation of 6-week fever, dyspnea, and cough, while case 2 was secondary to systemic lupus erythematosus and fever was the major symptom. Their chest CT scans revealed bilateral multiple consolidations, predominantly in the lower lobes. Both cases were initially diagnosed with pneumonia, but did not improve after treatment with broad-spectrum antibiotics. In both cases, transbronchial biopsy and bronchoalveolar lavage fluid examination were inconclusive and the pathological diagnosis was confirmed by percutaneous lung biopsy. Both patients had a good clinical response to prednisone. CONCLUSIONS: We report two rare AFOP cases to highlight the importance of awareness of this disease. We further perform the most comprehensive review to date in AFOP, including 150 patients since 2002. Consolidation was the most common imaging pattern, followed by ground-glass opacity and nodules. A lung biopsy is required for a definitive diagnosis. Corticosteroids is recommended as the most effective therapy, but treatment options should depend on the etiology and disease severity.