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2.
BMJ Open Respir Res ; 7(1)2020 09.
Article in English | MEDLINE | ID: mdl-32963028

ABSTRACT

Reviews of COVID-19 CT imaging along with postmortem lung biopsies and autopsies indicate that the majority of patients with COVID-19 pulmonary involvement have secondary organising pneumonia (OP) or its histological variant, acute fibrinous and organising pneumonia, both well-known complications of viral infections. Further, many publications on COVID-19 have debated the puzzling clinical characteristics of 'silent hypoxemia', 'happy hypoxemics' and 'atypical ARDS', all features consistent with OP. The recent announcement that RECOVERY, a randomised controlled trial comparing dexamethasone to placebo in COVID-19, was terminated early due to excess deaths in the control group further suggests patients present with OP given that corticosteroid therapy is the first-line treatment. Although RECOVERY along with other cohort studies report positive effects with corticosteroids on morbidity and mortality of COVID-19, treatment approaches could be made more effective given that secondary OP often requires prolonged duration and/or careful and monitored tapering of corticosteroid dose, with 'pulse' doses needed for the well-described fulminant subtype. Increasing recognition of this diagnosis will thus lead to more appropriate and effective treatment strategies in COVID-19, which may lead to a further reduction of need for ventilatory support and improved survival.


Subject(s)
Coronavirus Infections/physiopathology , Cryptogenic Organizing Pneumonia/diagnosis , Diagnostic Errors , Hypoxia/physiopathology , Lung/diagnostic imaging , Pneumonia, Viral/physiopathology , Betacoronavirus , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Cryptogenic Organizing Pneumonia/drug therapy , Cryptogenic Organizing Pneumonia/etiology , Cryptogenic Organizing Pneumonia/physiopathology , Dexamethasone/therapeutic use , Glucocorticoids/therapeutic use , Humans , Hypoxia/etiology , Lung/pathology , Lung/physiopathology , Lung Diseases, Interstitial/diagnosis , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/etiology , Lung Diseases, Interstitial/physiopathology , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , SARS-CoV-2 , Tomography, X-Ray Computed
4.
Eur Radiol ; 30(5): 2722-2730, 2020 May.
Article in English | MEDLINE | ID: mdl-32040727

ABSTRACT

OBJECTIVES: To investigate CT imaging features associated with poor clinical outcome after corticosteroid treatment in patients diagnosed with cryptogenic organizing pneumonia (COP) and connective tissue disease-related organizing pneumonia (CTD-OP) and to assess the difference in CT findings and treatment responses between COP and CTD-OP. METHODS: Chest CT images from 166 patients (COP, 131; CTD-OP, 35) with pathologically proven organizing pneumonia were reviewed by two thoracic radiologists. The type, distribution pattern, and extent of parenchymal abnormalities, along with other associated imaging features, were assessed for each patient. Logistic regression analyses were used to identify features associated with poor clinical outcomes such as residual disease (RD) and disease relapse. The differences between COP and CTD-OP were also analyzed. RESULTS: Consolidation involving more than 10% of parenchyma (hazard ratio [HR], 2.27), detectable bronchiectasis (HR, 3.59), and diagnosis of CTD-OP (HR, 4.31) were associated with a higher risk of RD after adjustments for patient age and sex. More than 10% consolidation involvement (HR, 2.54) and diagnosis of CTD-OP (HR, 6.42) were also associated with a higher risk of disease relapse. Compared with COP, CTD-OP demonstrated a greater extent of parenchymal abnormalities, especially consolidation, and was less likely to show a peribronchovascular distribution pattern. CONCLUSION: Bronchiectasis and a greater extent of consolidation were associated with RD, with the latter also being associated with disease relapse. Compared with COP, CTD-OP was associated with worse treatment outcomes and demonstrated a greater extent of parenchymal abnormalities, which were also less likely to show a peribronchovascular pattern. KEY POINTS: • The presence of bronchiectasis and a high parenchymal involvement of consolidation on initial chest CT were associated with a worse response to corticosteroids in patients with organizing pneumonia. • Connective tissue disease-related organizing pneumonia (CTD-OP) was associated with worse treatment outcomes than its idiopathic counterpart cryptogenic organizing pneumonia (COP). • Compared with COP, CTD-OP generally demonstrated a greater extent of parenchymal abnormalities, especially consolidation, and was less likely to show a peribronchovascular distribution pattern.


Subject(s)
Bronchiectasis/diagnostic imaging , Connective Tissue Diseases/complications , Cryptogenic Organizing Pneumonia/diagnostic imaging , Lung Diseases, Interstitial/diagnostic imaging , Adrenal Cortex Hormones/therapeutic use , Aged , Arthritis, Rheumatoid/complications , Cryptogenic Organizing Pneumonia/drug therapy , Cryptogenic Organizing Pneumonia/physiopathology , Dermatomyositis/complications , Female , Humans , Lung/diagnostic imaging , Lung/physiopathology , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/etiology , Lung Diseases, Interstitial/physiopathology , Male , Middle Aged , Prognosis , Proportional Hazards Models , Pulmonary Diffusing Capacity , Recurrence , Scleroderma, Systemic/complications , Tomography, X-Ray Computed , Total Lung Capacity , Treatment Outcome , Vital Capacity
5.
Biomed Pharmacother ; 118: 109380, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31545224

ABSTRACT

BACKGROUND: Corticosteroid is one of the main treatments for interstitial lung disease (ILD). Cryptogenic-organizing pneumonia (COP) is sensitive to corticosteroid therapy, whereas idiopathic pulmonary fibrosis (IPF) is not. Glucocorticoid receptor-α (GR-α) and histone deacetylase 2 (HDAC2) play critical roles in the sensitivity to corticosteroid therapy; however, it is unclear whether HDAC2 and/or GR-α are expressed in the lung tissues of patients with COP and/or IPF. Possible aberrant expressions of HDAC2 and GR-α in IPF and COP were investigated in the current study. METHODS: Lung tissue samples were obtained from patients with COP (n = 9), IPF (n = 8), pulmonary abscesses (n = 7), or pulmonary inflammatory pseudotumors (n = 6) before corticosteroid treatment, as well as from control subjects (n = 10). The expression of GR-α, HDAC2, PI3K-δ, and NF-κBp65 in the samples was assessed by immunohistochemistry. RESULTS: GR-α expression was the same in lung tissues from COP patients and control subjects, but was significantly lower in lung tissue from IPF. In addition, HDAC2 was significantly higher in lung tissues of COP patients compared to both IPF and control subjects. Furthermore, the transcription factor NF-κBp65 was significantly lower in lung tissues from both COP and control compared to IPF subjects, whereas there was no difference in NF-κBp65 when comparing tissues from COP patients to controls. HDAC2 and GR-α were negatively correlated with NF-κBp65 in COP lung tissue. CONCLUSION: HDAC2 and GR-α expression in lung tissues are potential biomarkers for predicting corticosteroid sensitivity when initially treating COP and IPF, as well as other forms of ILD.


Subject(s)
Histone Deacetylase 2/metabolism , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/metabolism , Receptors, Glucocorticoid/metabolism , Steroids/therapeutic use , Cryptogenic Organizing Pneumonia/complications , Cryptogenic Organizing Pneumonia/pathology , Cryptogenic Organizing Pneumonia/physiopathology , Female , Humans , Lung/pathology , Lung/physiopathology , Lung Diseases, Interstitial/physiopathology , Male , Middle Aged , Phosphatidylinositol 3-Kinases/metabolism , Transcription Factor RelA/metabolism
6.
Chron Respir Dis ; 16: 1479973119853829, 2019.
Article in English | MEDLINE | ID: mdl-31159568

ABSTRACT

Cryptogenic organizing pneumonia (COP) is characterized by good response to corticosteroids, but frequent relapses after reduction or cessation of treatment are noted. The incidence, risk factors of relapse, and long-term outcomes of patients with COP remain undetermined. Patients with COP from September 2010 to December 2017 were enrolled. Hospital and office records were used as data sources. Clinical information, lab examinations, chest radiographs, treatment courses, and follow-up data were collected. Relapse group was defined as worsening of clinical manifestations in combination with progression of radiographic abnormalities in the absence of identified causes. Eighty-seven patients with COP were enrolled. Of them, 73 patients were treated with corticosteroids with relapse rate yielding 31.5% (23 of 73). Eleven patients were treated with macrolides and none of them relapsed. Fever was more common (65.2% vs. 32.0%, p = 0.004), C-reactive protein (CRP) was higher (31.5 ± 39.4 mg/L vs. 17.5 ± 32.2 mg/L, p = 0.038), and diffusion capacity for carbon monoxide (DLCO) % predicted was lower (45.9 ± 14.2% vs. 57.6 ± 18.5%, p = 0.050) in relapse group compared to nonrelapse group. Four patients who presented with organizing pneumonia (OP) as the first manifestation were ultimately diagnosed with OP secondary to autoimmune disease in follow-up. We showed relapse was common in COP patients treated with corticosteroids, but the prognosis was favorable. Fever, elevated CRP, and a reduced DLCO were related to relapse. As OP may not always be cryptogenic, a careful follow-up should be programmed to diagnose the underlying systemic disease.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Autoimmune Diseases/diagnosis , Cryptogenic Organizing Pneumonia/drug therapy , Glucocorticoids/therapeutic use , Lung Diseases, Interstitial/diagnosis , Macrolides/therapeutic use , Adult , Aged , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Autoimmune Diseases/complications , Azithromycin/therapeutic use , C-Reactive Protein/metabolism , Clarithromycin/therapeutic use , Cryptogenic Organizing Pneumonia/diagnostic imaging , Cryptogenic Organizing Pneumonia/epidemiology , Cryptogenic Organizing Pneumonia/physiopathology , Diagnostic Errors , Female , Humans , Incidence , Longitudinal Studies , Lung/diagnostic imaging , Lung Diseases, Interstitial/etiology , Male , Middle Aged , Polymyositis/complications , Polymyositis/diagnosis , Prednisone/therapeutic use , Pulmonary Diffusing Capacity , Recurrence , Retrospective Studies , Risk Factors , Tomography, X-Ray Computed , Vital Capacity
7.
Zhonghua Jie He He Hu Xi Za Zhi ; 42(5): 361-366, 2019 May 12.
Article in Chinese | MEDLINE | ID: mdl-31137112

ABSTRACT

Objective: To explore the role of histone deacetylases(HDAC) in the pathogenesis of idiopathic pulmonary fibrosis(IPF) and cryptogenic organizing pneumonia(COP). Methods: Fifteen IPF patients [14 males and 1female, age 40-73 years, mean age (59±8) years] and 15 COP patients [5 males and 10 females, age 41-71 years, mean age (59±8) years] from Peking Union Medical College Hospital were recruited from March 2018 to October 2018. Fifteen healthy donors[4 males and 11females, age 43-70 years, mean age (58±6) years] were enrolled as controls. Peripheral blood mononuclear cells (PBMC) were isolated by density gradient centrifugation. The nuclear and cytoplasmic proteins were extracted by Nuclear Extraction Kit. HDAC activity was measured by fluorimetric method. The relations between HDAC activity and clinical parameters were analyzed with SPSS. Results: The HDAC activity of cytoplasmic protein and nuclear protein from patients with IPF were (724±216) nmol/L and (2 309±708) nmol/L, which were higher than that of health controls (409±105) nmol/L and (1 572±611) nmol/L (P<0.01 for both). So as to the HDAC activity of cytoplasmic protein and nuclear protein from patients with COP which were (718±245) nmol/L and (3 310±1 005) nmol/L (P<0.01 for both).The HDAC activity of nuclear protein from COP patients was higher than that from IPF patients (Z=-2.840, P=0.005). The HDAC activity of nuclear protein was negatively correlated with FEV(1) and D(L)CO in IPF patients (r=-0.574, P=0.025; r=-0.583, P=0.029), and negatively correlated with FVC and TLC in COP patients(r=-0.846, P=0.016; r=-0.900, P=0.015). Conclusion: HDAC may be involved in the pathogenesis of COP and IPF.


Subject(s)
Cryptogenic Organizing Pneumonia/physiopathology , Histone Deacetylases/blood , Idiopathic Pulmonary Fibrosis/physiopathology , Adult , Aged , Case-Control Studies , Cryptogenic Organizing Pneumonia/metabolism , Female , Humans , Idiopathic Pulmonary Fibrosis/metabolism , Leukocytes, Mononuclear , Male , Middle Aged
8.
BMC Pulm Med ; 19(1): 10, 2019 Jan 09.
Article in English | MEDLINE | ID: mdl-30626371

ABSTRACT

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.


Subject(s)
Cryptogenic Organizing Pneumonia/diagnosis , Lung/diagnostic imaging , Tomography, X-Ray Computed , Aged , Aged, 80 and over , Cryptogenic Organizing Pneumonia/drug therapy , Cryptogenic Organizing Pneumonia/physiopathology , Female , Humans , Japan , Lung/physiopathology , Male , Multivariate Analysis , Outcome Assessment, Health Care , Predictive Value of Tests , Proportional Hazards Models , Recurrence , Retrospective Studies , Risk Factors , Steroids/therapeutic use
9.
Respirology ; 23(3): 325-330, 2018 03.
Article in English | MEDLINE | ID: mdl-28960643

ABSTRACT

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.


Subject(s)
Cryptogenic Organizing Pneumonia/diagnosis , Lung/diagnostic imaging , Radiography, Thoracic/methods , Tomography, X-Ray Computed/methods , Adult , Aged , Cryptogenic Organizing Pneumonia/physiopathology , Disease Progression , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Respiratory Function Tests , Severity of Illness Index , Time Factors
10.
Cancer Radiother ; 21(5): 411-423, 2017 Aug.
Article in French | MEDLINE | ID: mdl-28596060

ABSTRACT

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.


Subject(s)
Cryptogenic Organizing Pneumonia/etiology , Cryptogenic Organizing Pneumonia/therapy , Pulmonary Fibrosis/etiology , Pulmonary Fibrosis/therapy , Radiation Injuries/therapy , Radiation Pneumonitis/therapy , Cryptogenic Organizing Pneumonia/diagnosis , Cryptogenic Organizing Pneumonia/physiopathology , Cryptogenic Organizing Pneumonia/prevention & control , Humans , Pulmonary Fibrosis/diagnosis , Pulmonary Fibrosis/physiopathology , Pulmonary Fibrosis/prevention & control , Radiation Injuries/diagnosis , Radiation Injuries/physiopathology , Radiation Injuries/prevention & control , Radiation Pneumonitis/diagnosis , Radiation Pneumonitis/physiopathology , Radiation Pneumonitis/prevention & control
11.
Intern Med ; 56(10): 1185-1191, 2017.
Article in English | MEDLINE | ID: mdl-28502934

ABSTRACT

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.


Subject(s)
Cryptogenic Organizing Pneumonia/diagnosis , Cryptogenic Organizing Pneumonia/physiopathology , Adrenal Cortex Hormones/therapeutic use , Aged , Cryptogenic Organizing Pneumonia/therapy , Female , Humans , Immunosuppressive Agents/therapeutic use , Prognosis , Respiration, Artificial
12.
Rheumatology (Oxford) ; 56(3): 344-350, 2017 03 01.
Article in English | MEDLINE | ID: mdl-27940586

ABSTRACT

Objective: To characterize a cohort of patients with RA who have interstitial lung disease (ILD) and to assess the utility of previously developed mortality staging systems [gender, age, lung physiology (GAP) and ILD-GAP]. Methods: All patients with RA and ILD seen at the Mayo Clinic from 1998 to 2014 were identified and manually screened for study inclusion. RA disease characteristics and pulmonary findings including high-resolution CT and pulmonary function testing were evaluated. Survival was estimated using Kaplan-Meier methods. GAP and ILD-GAP models were evaluated using c-statistics and standardized incidence ratios. Results: The study included 181 patients with RA-associated ILD (96% Caucasian; 48% females; 37% never-smokers). The mean age at ILD diagnosis was 67.4 years ( s . d . 9.9). The median time from RA diagnosis to ILD was 4.9 years (range -10.9-48.1). The median follow-up was 3.1 years (range 0.01-14.8). Age, RA disease duration and low initial diffusing capacity for carbon monoxide were predictive of premature mortality in multivariate modelling. Sex, smoking status, obstructive lung disease, seropositivity and erosive disease were not associated with mortality. The 5-year survival rate was 59.7% (95% CI 51.5, 69.2). Survival did not differ between usual interstitial pneumonia, non-specific interstitial pneumonia and organizing pneumonia ( P = 0.42). The GAP model performed well in this cohort for both discrimination and calibration (c-statistic 0.71, standardized incidence ratio 0.97). Conclusion: In this large single-centre cohort of patients with RA-ILD, most patients were seropositive and had a history of smoking. ILD most commonly occurred after the RA diagnosis. Mortality was high and did not differ among the types. The GAP model may be useful in assessing mortality risk.


Subject(s)
Arthritis, Rheumatoid/epidemiology , Lung Diseases, Interstitial/epidemiology , Age Factors , Aged , Arthritis, Rheumatoid/immunology , Cohort Studies , Comorbidity , Cryptogenic Organizing Pneumonia/diagnostic imaging , Cryptogenic Organizing Pneumonia/epidemiology , Cryptogenic Organizing Pneumonia/mortality , Cryptogenic Organizing Pneumonia/physiopathology , Female , Humans , Idiopathic Pulmonary Fibrosis/diagnostic imaging , Idiopathic Pulmonary Fibrosis/epidemiology , Idiopathic Pulmonary Fibrosis/mortality , Idiopathic Pulmonary Fibrosis/physiopathology , Incidence , Kaplan-Meier Estimate , Lung Diseases, Interstitial/diagnostic imaging , Lung Diseases, Interstitial/mortality , Lung Diseases, Interstitial/physiopathology , Male , Middle Aged , Multivariate Analysis , Pulmonary Diffusing Capacity , Respiratory Function Tests , Retrospective Studies , Rheumatoid Factor/immunology , Smoking/epidemiology , Survival Rate , Tomography, X-Ray Computed
13.
Chest ; 151(2): 389-399, 2017 02.
Article in English | MEDLINE | ID: mdl-27729263

ABSTRACT

BACKGROUND: Surgical lung biopsy (SLB) is invasive and not possible in all patients with undiagnosed interstitial lung disease (ILD). We hypothesized that transbronchial biopsy (TBB) findings combined with clinical and high-resolution CT (HRCT) data leads to a confident diagnosis congruent to SLB and therefore avoids the need for SLB in some patients. METHODS: We evaluated 33 patients being investigated for suspected ILD who underwent HRCT, TBB, and SLB. First, clinicians, radiologists, and a pathologist reviewed the clinical information and HRCT and TBB findings. Clinicians were asked to provide a diagnosis and were also asked if SLB was needed for a more confident diagnosis. Subsequently, the clinical, HRCT, and SLB data were reviewed, and the same participants were asked to provide a final diagnosis. Clinician consensus and overall agreement between TBB- and SLB-based diagnoses were calculated. RESULTS: Four patients had definite usual interstitial pneumonia (UIP) on HRCT and would not be considered for biopsy using current guidelines. Of the 29 patients without a definitive HRCT diagnosis, the clinicians felt confident of the diagnosis (ie, would not recommend SLB) in six cases. In these cases, there was 100% agreement between TBB and SLB diagnoses. UIP was the most common diagnosis (n = 3) and was associated with an HRCT diagnosis of possible UIP/nonspecific interstitial pneumonia-like. Agreement was poor (33%) between TBB and SLB diagnoses when confidence in the TBB diagnosis was low. CONCLUSIONS: Information from TBB, when combined with clinical and HRCT data, may provide enough information to make a confident and accurate diagnosis in approximately 20% to 30% of patients with ILD.


Subject(s)
Biopsy/methods , Bronchoscopy/methods , Lung Diseases, Interstitial/pathology , Lung/pathology , Adult , Aged , Alveolitis, Extrinsic Allergic/diagnostic imaging , Alveolitis, Extrinsic Allergic/pathology , Alveolitis, Extrinsic Allergic/physiopathology , Bronchiolitis/diagnostic imaging , Bronchiolitis/pathology , Bronchiolitis/physiopathology , Cohort Studies , Cryptogenic Organizing Pneumonia/diagnostic imaging , Cryptogenic Organizing Pneumonia/pathology , Cryptogenic Organizing Pneumonia/physiopathology , Female , Forced Expiratory Volume , Humans , Idiopathic Pulmonary Fibrosis/diagnostic imaging , Idiopathic Pulmonary Fibrosis/pathology , Idiopathic Pulmonary Fibrosis/physiopathology , Lung/physiopathology , Lung/surgery , Lung Diseases, Interstitial/diagnostic imaging , Lung Diseases, Interstitial/physiopathology , Male , Middle Aged , Pulmonary Diffusing Capacity , Retrospective Studies , Tomography, X-Ray Computed , Vital Capacity
14.
Adv Clin Exp Med ; 25(5): 871-878, 2016.
Article in English | MEDLINE | ID: mdl-28028949

ABSTRACT

BACKGROUND: Inflammatory cytokines are involved in the development of cryptogenic organizing pneumonia (COP). It has been shown that macrolides inhibit cytokine production in the alveolar macrophages of COP patients. OBJECTIVES: The aim of the study was to assess the concentrations of interleukin 1ß (IL-1ß), IL-6, IL-8 and transforming growth factor ß (TGF-ß) in serum and in bronchoalveolar lavage fluid (BAL-f) in COP patients treated with clarithromycin (CAM). MATERIAL AND METHODS: The study involved 26 patients (18 women and 8 men, mean age 56.46 ± 8.83 years) with biopsy-proven COP. After being treated with CAM, a complete recovery was achieved in 22 patients, while four patients did not respond to the treatment. The ELISA method was used to measure the serum and BAL-f concentrations of IL-1ß, IL-6, IL-8 and TGF-ß. RESULTS: Before treatment, the serum IL-1ß1, IL-6, IL-8 and TGF-ß1 concentrations were similar in responders and non-responders. Significant decreases in serum concentrations of IL-6 (8.98 ± 13.26 pg/mL vs. 3.1 ± 6.95 pg/mL; p = 0.005), IL-8 (20.14 ± 25.72 pg/mL vs. 10.14 ± 6.8 pg/mL; p = 0.007) and TGF-ß1 (37.89 ± 12.49 ng/mL vs. 26.49 ± 12.45 ng/mL; p = 0.001) were found after treatment, as well as a significant decrease in the BAL-f concentration of IL-6 (30.56 ± 56.78 pg/mL vs. 4.53 ± 5.84 pg/mL; p = 0.036). Clarithromycin treatment resulted in a significantly lower mean value of serum IL-6 responders than non-responders. CONCLUSIONS: In COP patients, response to clarithromycin treatment was associated with decreases in serum concentrations of IL-6, IL-8 and TGF-ß, and of rations, and of the BAL-f concentration of IL-6.


Subject(s)
Bronchoalveolar Lavage Fluid/chemistry , Clarithromycin/therapeutic use , Cryptogenic Organizing Pneumonia/blood , Cryptogenic Organizing Pneumonia/drug therapy , Interleukin-6/blood , Adult , Aged , Clarithromycin/pharmacology , Cryptogenic Organizing Pneumonia/diagnostic imaging , Cryptogenic Organizing Pneumonia/physiopathology , Female , Humans , Male , Middle Aged , Respiratory Function Tests
15.
BMJ Case Rep ; 20162016 Apr 06.
Article in English | MEDLINE | ID: mdl-27053543

ABSTRACT

Bleomycin-induced lung injury is the most common chemotherapy-associated lung disease, and is linked with several histopathological patterns. Acute fibrinous and organising pneumonia (AFOP) is a relatively new and rare histological pattern of diffuse lung injury. We report the first known case of bleomycin-induced AFOP. A 36-year-old man with metastatic testicular cancer received three cycles of bleomycin, etoposide and cisplatin, before being transitioned to paclitaxel, ifosfamide and cisplatin. He subsequently presented with exertional dyspnoea, cough and pleuritic chest pain. CT of the chest demonstrated bilateral ground glass opacities with peribronchovascular distribution and pulmonary function tests demonstrated a restrictive pattern of lung disease with impaired diffusion. Transbronchial biopsy revealed intra-alveolar fibrin deposits with organising pneumonia, consisting of intraluminal loose connective tissue consistent with AFOP. The patient received high-dose corticosteroids with symptomatic and radiographic improvement. AFOP should be recognised as a histopathological variant of bleomycin-induced lung injury.


Subject(s)
Bleomycin/adverse effects , Cryptogenic Organizing Pneumonia/chemically induced , Lung Injury/chemically induced , Testicular Neoplasms/drug therapy , Adrenal Cortex Hormones/therapeutic use , Adult , Bleomycin/therapeutic use , Cryptogenic Organizing Pneumonia/diagnostic imaging , Cryptogenic Organizing Pneumonia/drug therapy , Cryptogenic Organizing Pneumonia/physiopathology , Diagnosis, Differential , Humans , Lung Injury/diagnostic imaging , Lung Injury/drug therapy , Lung Injury/physiopathology , Male , Pneumonia , Respiratory Function Tests , Treatment Outcome
16.
BMJ Case Rep ; 20162016 Jan 29.
Article in English | MEDLINE | ID: mdl-26825933

ABSTRACT

A 14-year-old girl who was known to have a seizure disorder and on lamotrigine treatment was admitted to the hospital, with a history of rash, fever and cough. Her condition deteriorated with clinical features suggestive of anticonvulsant hypersensitivity syndrome (ACHS) complicated with bronchiolitis obliterans organising pneumonia (BOOP). Her chest CT showed multifocal parenchymal opacities and lung biopsy was typical for BOOP. Initially, the lamotrigine was discontinued since the onset of the rash, then she was treated for pneumonia with antibiotics, which may have delayed the diagnosis. Eventually, BOOP was considered and she was treated with a high dose of corticosteroid. She improved clinically and her repeated chest CT showed a marked resolution of the lesions. This case illustrates the possible occurrence of BOOP as a complication of ACHS secondary to lamotrigine treatment.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Anticonvulsants/adverse effects , Cryptogenic Organizing Pneumonia/chemically induced , Drug Hypersensitivity Syndrome/etiology , Epilepsy/drug therapy , Lung/drug effects , Lung/pathology , Triazines/adverse effects , Adolescent , Anticonvulsants/administration & dosage , Cryptogenic Organizing Pneumonia/diagnostic imaging , Cryptogenic Organizing Pneumonia/physiopathology , Female , Humans , Lamotrigine , Lung/diagnostic imaging , Tomography, X-Ray Computed , Treatment Outcome , Triazines/administration & dosage
17.
J Med Case Rep ; 10: 15, 2016 Jan 20.
Article in English | MEDLINE | ID: mdl-26791087

ABSTRACT

BACKGROUND: Myelodysplasia syndrome is a heterogeneous group of hematological disorders that are characterized by abnormal morphology and cytopenias of bone marrow elements. Azacitidine is a hypomethylating agent that is commonly used in treatment of myelodysplasia syndrome. We present an extremely rare case of cryptogenic organizing pneumonia following therapy with azacitidine and a review of the relevant literature. This is the fifth case of azacitidine-induced interstitial lung disease and the sixth one due to hypomethylating drugs; of interest, this is the first reported case that has occurred after the second cycle. Our case report highlights an important, potentially treatable and rare side effect of azacitidine and hypomethylating agents in general that might be overlooked by oncologists. Furthermore, our review of the literature showed heterogeneity in the clinical outcome which might, in part, be due to delay in initiating corticosteroids treatment. CASE PRESENTATION: A 67-year-old white man presented with worsening shortness of breath and mild productive cough that started 1 week prior to his presentation. An initial chest X-ray showed infiltration of both lung fields. Radiographic findings of computed axial tomography, results of bronchoscopy and a lung biopsy were consistent with cryptogenic organizing pneumonia. The patient showed variable clinical response to steroids and he remained dependent on home oxygen. CONCLUSIONS: We concluded that there is a recognizable potentially life-threatening toxicity due to organizing pneumonia secondary to azacitidine in the setting of myelodysplasia syndrome treatment. This toxicity is not limited to the first cycle as in previous cases; furthermore, pleural effusion can be associated with this toxicity. Health care professionals should be aware of this recognizable side effect. Early recognition and timely management are critical to prevent permanent lung fibrosis.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Antimetabolites, Antineoplastic/adverse effects , Azacitidine/adverse effects , Cryptogenic Organizing Pneumonia/chemically induced , Lung/pathology , Myelodysplastic Syndromes/drug therapy , Antimetabolites, Antineoplastic/administration & dosage , Azacitidine/administration & dosage , Bronchoscopy/methods , Cough/etiology , Cryptogenic Organizing Pneumonia/complications , Cryptogenic Organizing Pneumonia/physiopathology , Cryptogenic Organizing Pneumonia/therapy , Home Care Services , Humans , Lung/diagnostic imaging , Lung/drug effects , Male , Middle Aged , Oxygen Inhalation Therapy , Radiography , Treatment Outcome
18.
Respiration ; 90(2): 155-9, 2015.
Article in English | MEDLINE | ID: mdl-26045243

ABSTRACT

Cryptogenic organizing pneumonia (COP) is an interstitial lung disease that is usually responsive to corticosteroid treatment. The treatment of COP has not been studied in randomized controlled trials; thus, treatment decisions are based on practice guidelines. We herein present, for the first time, 4 cases of patients with biopsy-proven COP who did not respond to corticosteroids but benefited from rituximab therapy. This report consists of a retrospective case series of patients who experienced steroid-resistant, biopsy-proven COP. Patients included in this case series suffered from acute or chronic COP and did not respond to corticosteroid treatment for a few weeks to months but later responded to rituximab. In a series of 4 patients, 1 patient had a complete radiological and clinical response after rituximab therapy, and the steroids could be gradually tapered. Three patients had a chronic course but had been able to lower steroid dosage or even discontinue the drug after being treated with rituximab. Since 40% of the patients with COP do not respond to or stay dependent on steroids, we think that even the ability to lower the steroid dosage by using rituximab as a steroid-sparing agent with a good safety profile is worth the effort. However, further studies are warranted.


Subject(s)
Cryptogenic Organizing Pneumonia , Glucocorticoids , Lung , Rituximab , Aged , Aged, 80 and over , Biopsy , Cryptogenic Organizing Pneumonia/diagnosis , Cryptogenic Organizing Pneumonia/drug therapy , Cryptogenic Organizing Pneumonia/physiopathology , Drug Resistance , Drug Substitution/methods , Female , Glucocorticoids/administration & dosage , Glucocorticoids/adverse effects , Humans , Immunologic Factors/administration & dosage , Immunologic Factors/adverse effects , Lung/diagnostic imaging , Lung/pathology , Male , Middle Aged , Patient Acuity , Radiography , Rituximab/administration & dosage , Rituximab/adverse effects , Treatment Outcome
19.
Int J Clin Exp Pathol ; 8(1): 511-6, 2015.
Article in English | MEDLINE | ID: mdl-25755741

ABSTRACT

BACKGROUND AND OBJECTIVE: Focal organizing pneumonia (FOP) is an uncommon disease. The etiology, and in particular the disease's relationship with infection and the incidence of idiopathic FOP, is relatively unknown. The aim of this study is to review clinical, radiological and pathological features of patients with organizing pneumonia (OP) presenting solitary lesions and to analyze possible causes. METHODS: We retrospectively reviewed 37 surgical lung biopsy or resection cases of pathologically confirmed FOP over a period of 10 years. RESULTS: Microscopically, 17 cases showed OP with neutrophilic infiltration or abscess, 11 with epithelioid cell granulomas or scattered multinucleated giant cells, 2 with greater eosinophilic infiltration, and the remaining 7 cases met the diagnostic criteria for pathological cryptogenic OP (COP). The 37 cases of FOP included 22 men and 15 women, aged 29-76 years, and 17 cases had a history of smoking. Cough, fever, sputum, chest or back pain and hemoptysis were the main symptoms. Seven cases were asymptomatic. The diameters of the lesions ranged from 0.2-6.0 cm (median, 3.0 cm). Fever (9/30), high-sensitivity C-reactive protein elevation (9/17) and abnormalities in pulmonary function test (8/24) existed in focal secondary OP (FSOP) patients, but these symptoms were rarely observed in focal COP (FCOP) (0/7, 1/7 and 0/7 cases, respectively). However, no statistically significant differences were found between the FSOP and FCOP. CONCLUSIONS: Histologically, secondary factors exist in the majority of FOP cases. Idiopathic FOP is found in a minority. With respect to secondary FOP, acute infection and granulomatous inflammation are the main causes. Surgical resection alone appears sufficient for the management of FOP.


Subject(s)
Cryptogenic Organizing Pneumonia/pathology , Lung/pathology , Adult , Aged , Cryptogenic Organizing Pneumonia/physiopathology , Cryptogenic Organizing Pneumonia/surgery , Female , Humans , Lung/physiopathology , Lung/surgery , Male , Middle Aged , Respiratory Function Tests , Retrospective Studies , Treatment Outcome
20.
J Assoc Physicians India ; 63(7): 54-7, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26731829

ABSTRACT

Organising pneumonia is a histopathological entity characterised by intra-alveolar buds of granulation tissue, intermixed myofibroblasts and connective tissue. Cryptogenic organising pneumonia (COP) is characterised by this particular histopathological pattern, along with typical clinical and imaging features, when no other underlying aetiology is found. COP (previously known as bronchiolitis obliterans organising pneumonia [BOOP]) is one of the rare variants of interstitial pneumonias. This condition is characterised by a rapid clinical and radiological improvement with steroid treatment. Here we are reporting a case of COP in adult female with discussion on approach and basic pathophysiology of this type of pneumonia.


Subject(s)
Cryptogenic Organizing Pneumonia/diagnosis , Cryptogenic Organizing Pneumonia/etiology , Cryptogenic Organizing Pneumonia/physiopathology , Female , Humans , Middle Aged
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