Interleukin-22 exacerbates airway inflammation induced by short-term exposure to cigarette smoke in mice.

AIM: Interleukin-22 (IL-22) exhibits both proinflammatory and anti-inflammatory properties in various biological processes. In this study we explored the effects of exogenous recombinant IL-22 (rIL-22) on cigarette smoke (CS)-induced airway inflammation in mice. METHODS: Male C57BL/6 mice were divided into groups: (1) CS group exposed to tobacco smoke for 3 consecutive days, (2) rIL-22 group received rIL-22 (100 mg/kg, ip), and (3) CS plus rIL-22 group, received rIL-22 (100 mg/kg, ip) before the CS exposure. The airway resistance (Rn), lung morphology, inflammatory cells in the airways, and inflammatory cytokines and CXCR3 ligands in both bronchoalveolar lavage (BAL) fluids and lung tissues were analyzed. RESULTS: CS alone significantly elevated IL-22 level in the BAL fluid. Both CS and rIL-22 significantly augmented airway resistance, an influx of inflammatory cells into the airways and lung parenchyma, and significantly elevated levels of pro-inflammatory cytokines (TGFß1 and IL-17A) and CXCR3 chemokines (particularly CXCL10) at the mRNA and/or protein levels. Furthermore, the effects of rIL-22 on airway resistance and inflammation were synergistic with those of CS, as demonstrated by a further increased Rn value, infiltration of greater numbers of inflammatory cells into the lung, higher levels of inflammatory cytokines and chemokines, and more severe pathological changes in CS plus rIL-22 group as compared to those in CS group. CONCLUSION: Exogenous rIL-22 exacerbates the airway inflammatory responses to CS exposure in part by inducing expression of several proinflammatory cytokines and CXCR3 ligands.

Characteristics of pulmonary inflammation in combined pulmonary fibrosis and emphysema.

BACKGROUND: The condition of concomitant upper lobe emphysema and lower lobe fibrosis as identified by computer tomography is known as combined pulmonary fibrosis and emphysema (CPFE). CPFE has distinct clinical characteristics compared with emphysema alone (EA) and idiopathic pulmonary fibrosis (IPF) without emphysema. However, the pulmonary inflammation characteristics of CPFE are not well known, and the differences between CPFE and the other two diseases with regards to pulmonary inflammation need to be explored. The pulmonary inflammatory characteristics were investigated in CPFE patients and compared with EA and IPF. METHODS: Fraction exhaled nitric oxide (Fe,NO) and differential cell counts, the concentrations of monokine induced by interferon gamma (MIG/CXCL9), interferon-inducible protein 10 (IP-10/CXCL10), and interferon-inducible T cell alpha chemoattractant (I-TAC/CXCL11) were measured in induced sputum obtained from subjects with CPFE (n = 22), EA (n = 22), IPF (n = 14), and healthy volunteers (HV, n = 12). In addition, immunohistochemistry was used to quantify the expression of nitric oxide synthases in alveolar macrophages in 23 lung tissues from patients and control subjects. RESULTS: The CPFE group had higher alveolar NO than subjects in the EA and HV groups (P = 0.009, P = 0.001, respectively) but not than the IPF group (P > 0.05). Numbers of sputum eosinophils were significantly elevated in CPFE and IPF groups compared with the HV group (P = 0.001, P = 0.008). In contrast, eosinophil counts in EA group did not differ from those in the HV group. Compared with the EA and HV groups, the CPFE group had a lower concentration of I-TAC/CXCL11 in sputum supernatants (P = 0.003, P = 0.004). Immunoreactivity for inducible nitric oxide synthase (iNOS) was higher in the CPFE group than in the EA group (P = 0.018, P = 0.006, respectively). CONCLUSIONS: The pulmonary inflammation of CPFE group is more similar to IPF group, while the distal airway inflammation is more significant in CPFE and IPF groups than in EA group. Lung eosinophil cell infiltration and high NOS expression in alveolar macrophage might participate in this pathogenesis.

Correlation of eosinophil counts in induced sputum and fractional concentration of exhaled nitric oxide and lung functions in patients with mild to moderate asthma.

BACKGROUND: The airway inflammation could be assessed by some noninvasive approaches. To investigate the value of eosinophil counts in induced sputum and fractional concentration of exhaled nitric oxide (FENO) for the regimen adjustment in patients with asthma, the correlation was analyzed between the two parameters and lung function parameter (forced expiratory volume in one second (FEV(1))). METHODS: Sixty-five outpatients with mild to moderate non-exacerbation asthma from Beijing Chao-Yang Hospital were enrolled as treatment group. Combined medications of inhaled corticosteroids plus long-acting beta-2 agonist were administered for one year. Lung function parameters, eosinophil counts in induced sputum, concentration of exhaled nitric oxide and the Asthma Control Test scores were recorded, at regular intervals in the follow-up period. Twenty-one healthy volunteers were enrolled as control group and underwent examination of eosinophil counts in induced sputum, lung function and concentration of exhaled nitric oxide. RESULTS: Sixty-three subjects from treatment group completed follow-up period for one year or longer. Mean FEV(1) value of the 63 subjects was (2.75 ± 0.54) L at baseline, (2.97 ± 0.56) L and (3.07 ± 0.52) L at month 3 and month 6, respectively, and maintained as (3.14 ± 0.51) L in the following six months. Mean FENO decreased from (61 ± 25) parts per billion (ppb) at baseline to (32 ± 19) ppb at month 3 (P < 0.05), and continued to decrease to (22 ± 12) ppb at month 6, the difference being significant when compared to both baseline and control group ((13 ± 8) ppb). Mean eosinophil counts decreased to (0.032 ± 0.011) × 10(6)/ml at month 3, which was significantly different from baseline ((0.093 ± 0.023)×10(6)/ml) and the control group ((0.005 ± 0.003)×10(6)/ml (both P < 0.05). The eosinophil counts in induced sputum correlated positively with concentration of FENO in the first six months (all P < 0.05). The concentration of FENO had a significant negative correlation with FEV(1) value (all P < 0.05) in any time point in the follow-up period. The Asthma Control Test scores were 18 ± 5, 19 ± 7, 23 ± 2, 24 ± 1 and 24 ± 1 at months 1, 3, 6, 9 and 12, respectively, which were significantly different from the score at baseline (14 ± 3) (P < 0.05). The most rapid clinical effect was observed at the second month after treatment. CONCLUSION: Eosinophil counts in induced sputum and FENO are sensitive parameters to detect airway inflammation and may be useful in evaluating the efficacy of treatment and adjusting medication regimens.

Clinical features of pneumonia caused by 2009 influenza A(H1N1) virus in Beijing, China.

BACKGROUND: Data on symptoms and radiographic changes in patients with pandemic 2009 influenza A(H1N1) (A[H1N1]) pneumonia during convalescence have not been reported. METHODS: During October 26, 2009, and January 23, 2010, adult patients with pneumonia with laboratory-confirmed or clinically suspected A(H1N1) infections were observed for clinical characteristics, high-resolution chest CT scan, and lung function test changes during acute and 3-month convalescent phases. RESULTS: Of the 65 case subjects, the median age was 41 (interquartile range [IQR], 28-57) years, 60.0% were men, and 55.4% had at least one underlying medical condition. Sixty-two patients started oseltamivir therapy within a median of 5 (IQR, 4-6) days from the onset of illness, and 31 received IV corticosteroids. ARDS developed in 33 patients, and 24 were treated initially with noninvasive positive pressure ventilation (NPPV). In this group, NPPV was successful in 13 patients (54.2%). Nine patients died at a median of 16 (IQR, 10-24) days after onset of illness. Multivariate Cox regression identified two independent risk factors for death: progressive dyspnea after resolution of fever (relative risk, 5.852; 95% CI, 1.395-24.541; P = .016) and a higher APACHE (Acute Physiology and Chronic Health Evaluation) II score on presentation (relative risk for each point, 1.312; 95% CI, 1.140-1.511; P < .001). At 3-month follow-up of survivors with A(H1N1), ground-glass opacities were still present, although diminished, in 85.7%, and diffusing capacity for carbon monoxide was mildly reduced in 61.5%. CONCLUSIONS: Ground-glass opacities and decreased diffusing capacity were the main abnormalities observed at 3-month follow-up of survivors of A(H1N1).

[A hospital-wide intervention program to optimize the utilization quality of carbapenems and glycopeptides].

OBJECTIVE: To investigate the impact of intervention program upon improvement of utilization quality of carbapenems and glycopeptides. METHODS: Multifaceted intervention program of carbapenems and glycopeptides was conducted at our hospital. It involved written justification forms, expert consultation committee meetings, audit, feedback and re-feedback. From November 1, 2007 until October 31, 2008, retrospective audit and feedback were performed on all patients dosed with carbapenems or glycopeptides. Case reports were reviewed and data of ratio of appropriate antibiotic use, length of hospital stay, total cost, mortality and rate of vancomycin-resistant Enterococci (VRE) were collected and compared between the first and second half year of antibiotic intervention program. RESULTS: A total of 397 cases were reviewed, 75 cases discussed at expert committee meetings and 58 feedback letters delivered to responsible doctors. The consumption of both carbapenems and glycopeptides decreased. The appropriate use of carbapenems and glycopeptides increased from 37.8% (45/119) to 53.5% (48/127, P < 0.05) and from 45.6% (36/79) to 63.9% (46/72, P < 0.05) respectively. The total cost and mortality of patients dosed with glycopeptides decreased from a median of RMB 65,700 (30,300 - 146,900) yuan to 55,700 (36,700 - 90,900) yuan, and from 39.2% to 26.4% respectively. The rate of VRE decreased from 5.63% in 2007 to 3.80% during the second half year of 2008. CONCLUSION: Antibiotic intervention program of carbapenems and glycopeptides is effective in decreasing the inappropriate antibiotic use.

[Airway inflammation and peripheral airway function in asthmatic patients with different control levels].

OBJECTIVE: To observe the airway inflammation and peripheral airway function in asthmatic patients with different control levels, and to investigate whether the airway inflammation profile detected by induced sputum reflects the peripheral airway dysfunction. METHODS: The recruited asthmatic subjects (n = 66) were divided into 3 groups: asthma controlled (8 male and 13 female), asthma partly controlled (12 male and 16 female), asthma uncontrolled (6 male and 11 female). Twenty healthy subjects served as the control group (9 male and 11 female). On the 1(st) day, all the subjects were required to take asthma control test (ACT), and to receive measurement of lung function by oscillometry and spirometry as well as inflammatory cell profile of induced sputum and the concentration of eosinophil cationic protein (ECP). Exhaled nitric oxide (FE(NO)) was measured on the 2(nd) day, and oscillometry methacholine provocation was conducted for patients whose baseline FEV(1) was > or = 70% predicted. The provocation process was terminated when airway resistance was increased by twice of the basic value, or when the methacholine reached the highest concentration. Then airway resistance and lung function were examined after 3 minutes. Finally, airway resistance and lung function were measured again after the subjects had 5 consecutive deep inspirations (DI). Correlation analysis was conducted between ACT scores and inflammatory cells count, ECP concentrations of induced sputum and FE(NO) among different groups. The correlations were also made between the change of peripheral airway resistance triggered by provocation or DI and ACT scores, total eosinophil, ECP level of induced sputum, FE(NO) respectively. RESULTS: The total eosinophil count and ECP level in induced sputum and FE(NO) in asthmatic patients increased with the decline of control level. Negative correlations between ACT scores and total eosinophil count as well as the ECP level were observed (r = -0.43, -0.56, P < 0.01). In the healthy control group, the percentage of increase in peripheral airway resistance (R(5)-R(20)) and central airway resistance (R(20)) did not show significant difference (F = 3.472, P > 0.05) with methacholine provocation, while the percentage of increase in R(5)-R(20) was greater than in R(20) in both controlled and partly controlled asthmatic patients with provocation (F = 18.09 and 14.14, P < 0.01), though the change of R(5)-R(20) showed no correlations with ACT scores, eosinophil count of induced sputum, ECP level and FE(NO). After DI, R(5)-R(20) decreased from (0.13 +/- 0.14) kPa x L(-1) x s(-1) to (0.08 +/- 0.09) kPa x L(-1) x s(-1) (t = 2.84, P < 0.05) in the healthy control group, while R(5)-R(20) increased from (0.24 +/- 0.15) kPa x L(-1) x s(-1) to (0.30 +/- 0.16) kPa x L(-1) x s(-1) in the controlled asthma group, from (0.31 +/- 0.18) kPa x L(-1) x s(-1) to (0.39 +/- 0.17) kPa x L(-1) x s(-1) in the partly controlled asthma group (t = 3.90 and 4.68, P < 0.01, respectively). No correlations were observed between the change of R(5)-R(20) after DI and ACT scores, total eosinophil counts, ECP level as well as FE(NO) (r = -0.07, 0.28, -0.14, 0.14, P > 0.05). CONCLUSIONS: Even in asthma patients with controlled disease, eosinophilic inflammation in the airway was still present, and the eosinophilic inflammation became more severe with the decline of control level. Bronchodilatory effect caused by DI disappeared in asthmatic patients. The inflammation profile detected by induced sputum did not reflect the dysfunction of peripheral airways.