Efficacy of corticosteroid treatment for severe community-acquired pneumonia: A meta-analysis.

BACKGROUND: The benefits and adverse effects of corticosteroids in the treatment of severe community-acquired pneumonia (CAP) have not been well assessed. The aim of this systematic review of the literature and meta-analysis was to evaluate the clinical efficacy of adjuvant corticosteroid therapy in patients with severe CAP. METHODS: The following databases were searched: PubMed, the Cochrane database, Embase, Wanfang, the China National Knowledge Infrastructure (CNKI), and the WeiPu (VIP) database in Chinese. Published randomized controlled clinical trial results were identified that compared corticosteroid therapy with conventional therapy for patients with severe CAP, up to November 2016. The relative risk (RR), weighted mean difference (WMD), and 95% confidence interval (CI) were evaluated. Statistical analysis was performed using STATA 10.0. The quality of the published studies was evaluated using the Oxford quality scoring system (Jadad scale). RESULTS: Ten randomized controlled trials (RCTs) were identified that included 729 patients with severe CAP. Data analysis showed that corticosteroid therapy did not have a statistically significant clinical effect in patients with severe CAP (RR: 1.19; 95% CI: 0.99-1.42), mechanical ventilation time (WMD: -2.30; 95% CI: -6.09-1.49). However, corticosteroids treatment was significantly associated with reduced in-hospital mortality (RR: 0.49; 95% CI: 0.29-0.85), reduced length of hospital stay (WMD: -4.21; 95% CI: -6.61 to -1.81). CONCLUSION: Corticosteroids adjuvant therapy in patients with severe CAP may reduce the rate of in-hospital mortality, reduce the length of hospital stay, and reduce CRP levels.

[Identification and classification of respiratory pacemaker neurons in the medial region of nucleus retrofacialis in neonatal rats.].

The aim of the present study is to supply direct experimental proof that the medial region of nucleus retrofacialis (mNRF) is the site generating basic rhythm of respiration. Medullary slices of neonatal Sprague-Dawley rats, including hypoglossal nerve root and mNRF, were made according to Suzue's method. Simultaneous recordings of the respiratory rhythmic discharge activity (RRDA) in hypoglossal nerve root with suction electrode and the respiratory neuronal discharge in the mNRF with whole cell patch clamp were performed on the brainstem slice in vitro. Not only the electrophysiological characteristics of pacemaker and non-pacemaker neurons, but the cadmium-sensitivity of pacemaker neurons was observed. The nature of the discharge in the respiratory pacemaker neurons in mNRF was spontaneous, rhythmical and voltage-dependent burst behavior, generating an ectopic burst in response to a depolarizing or hyperpolarizing current. There were no significant differences in capacitance of membrane (C(m)), input resistance of membrane (R(m)) and leak inward current (I(leak)) between the pacemaker neurons and the non-pacemaker ones. Moreover, most pacemaker neurons in the mNRF were Cd(2+)-insensitive. In conclusion, these results support the idea that the mNRF is the site generating basic respiratory rhythm.

[Clinical analysis of 25 cases of biopsy-proven cryptogenic organizing pneumonia].

OBJECTIVE: To analyze the clinical, radiological and pathological features, diagnosis and response to therapy as well as prognosis of 25 cases of cryptogenic organizing pneumonia (COP). METHODS: Twenty-five subjects with COP confirmed by lung biopsy in Shanghai Pulmonary Hospital from January of 2000 to April of 2006 were retrospectively reviewed. Secondary reaction to infections, drugs, radiation, connective tissue diseases and various noxious agents were excluded. Their clinical-pathological characteristics, radiological features, response to treatment, relapse, survival were obtained from medical records and a follow-up patient questionnaire. RESULTS: There were 6 males and 19 females, with a mean age of 56 years (range 40 - 73 years). The presentations included cough (25/25), clear sputum (21/25), dyspnea (17/25), hemoptysis (5/25), fever and sweats (3/25), and "Velcro" crackles (18/25). Four of them were smokers, 11 had allergic reaction to some drugs, and 11 had some industrious dust inhalation. In 23 cases the specimens were obtained by video-assisted thoracoscopy and 2 cases by transbronchial lung biopsy. Bilateral lung involvement was present in 23 cases and all of them had at least two different radiological manifestations. Twenty-four cases showed a sub-pleural distribution. Bilateral patchy alveolar and ground glass involvement were found in 8 cases, airspace consolidation in 8 cases, mass in 11 cases, irregular lines in 10 cases, small nodules (<10 mm) in 4 cases. Two patients received operation. Corticosteroid therapy was administered to 23 patients. Seventeen cases were cured, but 8 of them relapsed after stopping (n = 2) and tapering (n = 6, when prednisone less than 5 - 10 mg/d) of corticosteroids within one to two years of therapy. CONCLUSIONS: COP is not very rare in China. The clinical-radiological-pathological diagnosis (CRP) is the most important diagnostic method. Corticosteroid is the first choice for COP therapy. The prognosis of COP is good if therapy is started in time, but relapse is common.

[Role of 5-HT2A-receptors coupled with superoxide anion in the medial area of nucleus retrofacialis].

OBJECTIVE: To explore the effect of 5-HT2A-receptors coupled with superoxide anion (O2-) on respiratory regulation signal transductionin passageway in the medial area of nucleus retrofacialis (mNRF). METHODS: mNRF island was prepared from medullary slices of neonatal SD rats according to Johnson's method and transferred separately into 24-well culture plates with reagents according to protocol, followed by incubation for 60 min at 37 degrees C in a humidified incubator with 5% CO2. Absorbance of 100 microl supernatant was measured by spectrophotometry at 550 nm and the effect of 5-HT and 2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI, agonist of 5-HT2A-receptors) on O2- generation in the mNRF was observed, along with the inhibition of this effect by ketanserin (antagonist of 5-HT2A-receptors) and alpha-lipoic acid (alpha-LA, a antioxidant). RESULTS: 5-HT concentration-response curve demonstrated that absorbance peak occurred at 1 micromol/L without further increment with higher concentration. DOI concentration-response curve showed the absorbance peak at 20 micromol/L without further increment. 5-HT and DOI significantly increased the absorbance with comparable effects. Ketanserin and alpha-LA significantly decreased the absorbance generated by 5-HT and DOI. CONCLUSION: Activation of 5-HT2A receptors results in obvious O2- production in mNRF, suggesting that 5-HT2A receptors regulate respiratory function in association with O2-.

[Comparative analysis of respiratory bronchiolitis-associated interstitial lung disease and desquamative interstitial pneumonia].

OBJECTIVE: To investigate the clinicopathologic characteristics of respiratory bronchiolitis-associated interstitial lung disease (RBILD) and its relationship to desquamative interstitial pneumonia (DIP). METHODS: The clinical and pathological data of one patient with RBILD confirmed by video-assisted thoracoscopic lung biopsy were reviewed retrospectively, and compared with one patient with DIP. RESULTS: Both patients were 57 year old male, and they had a history of cigarette smoking for 24 and 30 years respectively. The clinical manifestations were cough and sputum production, breathlessness with exertion, and crackles on chest examination. Lung function test showed a mild abnormality with mixed obstructive-restrictive and restrictive pattern respectively. The chest radiograph showed scattered small nodules and patchy densities. High resolution computer tomography showed scattered interstitial infiltrates and reticular changes in the middle and lower lung fields, but patchy ground-glass attenuation was found only in DIP. The pathological examination showed the presence of clusters of pigmented macrophages within the lumens of respiratory bronchioles, alveolar ducts and peribronchiolar alveolar spaces, with patchy submucosal and peribronchiolar infiltration of lymphocytes and histiocytes. Mild peribronchiolar fibrosis was found in RBILD. Compared with RBILD, the lesions of DIP were more severe and widespread. Both the patients responded favorably to glucocorticoids. They were followed for more than three years. CONCLUSION: RBILD could be confused with DIP in clinical manifestations, but can be separated by open lung biopsy. Considering their similarities, these two lesions may be regarded as a same disease entity.

[Clinicopathologic features of usual interstitial pneumonia and its differential diagnosis from idiopathic nonspecific interstitial pneumonia].

OBJECTIVE: To investigate the clinicopathologic features of usual interstitial pneumonia (UIP) and its differential diagnosis from idiopathic nonspecific interstitial pneumonia (INSIP). METHODS: The clinical and pathological features of 15 UIP and 11 cases of INSIP, having received open or video-assisted thoracoscopic lung biopsies and having follow-up information were reviewed. RESULTS: UIP occurred more often in males over 50 years of age. Clinical findings included progressive shortness of breath, cough, sputum and crackles over both lung fields. High resolution computerized tomography (HRCT) showed patchy attenuation, especially over both lower lobes. Honeycombing was found in 8 cases. Histologically, UIP was characterized by scattered fibrotic foci, fibrosis (often associated with honeycombing) and pulmonary architectural destruction. It had a heterogeneous appearance, with alternating areas of normal lung, interstitial inflammation, fibrosis and honeycomb changes. The frequencies of fibroblastic foci, muscle sclerosis, honeycomb changes, diffuse fibrosis and pulmonary architectural destruction in UIP and INSIP were 100% and 27.3% (P<0.001), 80.0% and 36.4% (P<0.05), 86.7% and 27.3% (P<0.001), 100% and 54.5% (P<0.01) and 100% and 45.5% (P<0.05), respectively. The response rate to glucocorticoid was 26.7% and 72.7% (P<0.05) in UIP and INSIP respectively. CONCLUSIONS: The distinction between UIP and INSIP is difficult if based on clinical examination alone. HRCT is helpful for differential diagnosis in some difficult cases. Definite diagnosis depends mainly on open lung biopsies. Key histologic features of UIP include heterogeneous appearance with interstitial inflammation, fibroblastic foci, scar formation and honeycomb changes.

The influence of dexamethasone on the proliferation and apoptosis of pulmonary inflammatory cells in bleomycin-induced pulmonary fibrosis in rats.

OBJECTIVE: The aim of this study was to investigate the inhibitory effect of dexamethasone on the state of proliferation/apoptosis of the pulmonary inflammatory cells in a rat pulmonary fibrosis model induced by bleomycin. METHODOLOGY: Seventy-five pathogen-free Sprague-Dawley (SD) rats were randomly divided into three groups: control, bleomycin (BLM) and dexamethasone (DXM) groups with 25 rats in each group. Each group was then divided into five subgroups based on time of study (1-, 3-, 7-, 14- and 28-days). BAL fluid was obtained, the cells were counted and a differential was performed. A lower DNA content in apoptotic cells was detected and quantitated by flow cytometry. Haematoxylin and eosin staining was performed to observe the extent of alveolitis and fibrosis of lung tissue; the morphological changes in apoptotic cells were discerned by transmission electron-microscopy and a semi-quantitative assessment of apoptotic cells in lung tissue was performed using in situ TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick endlabelling). RESULTS: The total number of inflammatory cells and the percentage of neutrophils in BAL fluid in almost every subgroup of the DXM group were significantly lower than those in corresponding subgroups of the BLM group (P < 0.01). The percentages of apoptotic cells in BAL fluid in the 14-day and 28-day subgroups of the DXM group were higher than those in corresponding subgroups of the BLM group (P < 0.05). The peak of alveolitis in the DXM group shifted backward and the extent of fibrosis was less than that in the BLM group. The apoptosis index (AI) of inflammatory cells in each of the DXM subgroups was higher than that in corresponding BLM subgroups except for day 14. CONCLUSION: Dexamethasone can induce apoptosis of pulmonary inflammatory cells and reduce the extent of alveolitis and fibrosis in bleomycin-induced pulmonary fibrosis of rats.

[Investigation of drug-resistance to rifampin and rpoB gene sequence analysis of Mycobacterium abscessus].

OBJECTIVE: To observe the resistance of Mycobacterium abscessus to rifampin and to investigate if there is any mutation of rpoB gene in strains with high minimal inhibitory concentration (MIC). METHODS: Mycobacterium abscessus was identified with both biochemical methods and PCR-RFLP. The MICs of rifampin to all the clinical strains and the type strain ATCC19977 were determined. DNA sequences were obtained from a 1272 bp fragment of the rpoB gene from either low or high rifampin MIC strains using PCR amplification. RESULTS: Only one strain had low MICs of 4 microg/ml. MICs of all the other 14 strains, as well as the type stain were above 128-256 microg/ml. Although there were some differences in nucleotide sequence of rpoB gene, all strains had the same amino acid sequence without any mutations. CONCLUSIONS: Mycobacterium abscessus showed a high resistance to rifampin. Mutations of rpoB gene do not seem to be the responsible mechanism.