Clinical significance of Pneumocystis jiroveci in patients with active tuberculosis

Pneumocystis colonization has been associated with airway inflammation and obstruction. We conducted a retrospective cohort study to investigate the clinical significance of Pneumocystis in the airway of patients with active tuberculosis. Of the 108 respiratory specimens tested positive for M. tuberculosis by polymerase chain reaction (PCR), 11 (10.2%) were also positive for Pneumocystis by PCR. Compared with patients tested negative for Pneumocystis, those with Pneumocystis had a higher serum alanine transaminase level, a greater likelihood of requiring oxygen supplementation, and a worse 30-day mortality. The proportion of patients with chronic obstructive pulmonary disease was not significantly different between the 2 groups, but lung malignancy was more prevalent among patients with Pneumocystis. Multivariate analysis showed that Pneumocystis was independently associated with oxygen supplementation. Our study has shown an association between the detection of Pneumocystis in lower respiratory tract specimens and greater impairment of pulmonary function among patients with active tuberculosis.     

基于体素观察慢性阻塞性肺疾病肺叶损伤程度及空间分布

目的 探讨基于体素定量CT分析慢性阻塞性肺疾病（COPD）患者肺叶损伤程度及空间分布的价值。方法 在"数字肺"多研究中心连续性纳入接受双气相扫描COPD患者，测定小气道病变（fSAD）和肺气肿（Emph）的定量值；分析患者各肺叶之间Emph、fSAD肺叶损伤程度及肺叶分布的差异，以及各肺叶定量CT分布与肺功能的相关性。结果 最终纳入50例COPD患者。Emph和fSAD均以右肺中叶最重，两肺上叶次之，两肺下叶程度最轻；Emph和fSAD均主要分布于左肺上叶，其次为右肺上叶，右肺中叶分布最少。两肺下叶Emph和fSAD与FEV₁%的相关性较好。结论 COPD患者肺叶损伤程度以右肺中叶及两肺上叶为重，尤其是右肺中叶；Emph和fSAD主要分布于左肺上叶，其次是右肺上叶；两肺下叶损伤对COPD患者肺功能的影响更著。     

Regional distribution of gas and tissue in acute respiratory distress syndrome. I. Consequences for lung morphology

Objective: To compare the computed tomographic (CT) analysis of the distribution of gas and tissue in the lungs of patients with ARDS with that in healthy volunteers. Design: Prospective study over a 53-month period.¶Setting: Fourteen-bed surgical intensive care unit of a university hospital. Patients and participants: Seventy-one consecutive patients with early ARDS and 11 healthy volunteers. Measurements and results: A lung CT was performed at end-expiration in patients with ARDS (at zero PEEP) and healthy volunteers. In patients with ARDS, end-expiratory lung volume (gas + tissue) and functional residual capacity (FRC) were reduced by 17 % and 58 % respectively, and an excess lung tissue of 701 ± 321 ml was observed. The loss of gas was more pronounced in the lower than in the upper lobes. The lower lobes of 27 % of the patients were characterized by “compression atelectasis,” defined as a massive loss of aeration with no concomitant excess in lung tissue, and “inflammatory atelectasis,” defined as a massive loss of aeration associated with an excess lung tissue, was observed in 73 % of the patients. Three groups of patients were differentiated according to the appearance of their CT: 23 % had diffuse attenuations evenly distributed in the two lungs, 36 % had lobar attenuations predominating in the lower lobes, and 41 % had patchy attenuations unevenly distributed in the two lungs. The three groups were similar regarding excess lung tissue in the upper and lower lobes and reduction in FRC in the lower lobes. In contrast, the FRC of the upper lobes was markedly lower in patients with diffuse or patchy attenuations than in healthy volunteers or patients with lobar attenuations. Conclusions: These results demonstrate that striking differences in lung morphology, corresponding to different distributions of gas within the lungs, are observed in patients whose respiratory condition fulfills the definition criteria of ARDS.     

Regional distribution of gas and tissue in acute respiratory distress syndrome. III. Consequences for the effects of positive end-expiratory pressure

Objective: To determine whether differences in lung morphology assessed by computed tomography (CT) affect the response to positive end-expiratory pressure (PEEP).¶Design: Prospective study over a 53-month period.¶Setting: Fourteen-bed surgical intensive care unit of a university hospital.¶Patients and participants: Seventy-one consecutive patients with early adult respiratory distress syndrome (ARDS).¶Measurements and results: Fast spiral thoracic CT was performed at zero end-expiratory pressure (ZEEP) and after implementation of PEEP 10 cmH₂O. Hemodynamic and respiratory parameters were measured in both conditions. PEEP-induced overdistension and alveolar recruitment were quantified by specifically designed software (Lungview). Overdistension occurred only in the upper lobes and was significantly correlated with the volume of lung, characterized by a CT attenuation ranging between –900 and –800 HU in ZEEP conditions. Cardiorespiratory effects of PEEP were similar in patients with primary and secondary ARDS. PEEP-induced alveolar recruitment of the lower lobes was significantly correlated with their lung volume (gas + tissue) at functional residual capacity. PEEP-induced alveolar recruitment was greater in the lower lobes with “inflammatory atelectasis” than in the lower lobes with “mechanical atelectasis.” Lung morphology as assessed by CT markedly influenced the effects of PEEP: in patients with diffuse CT attenuations PEEP induced a marked alveolar recruitment without overdistension, whereas in patients with lobar CT attenuations PEEP induced a mild alveolar recruitment associated with overdistension of previously aerated lung areas. These results can be explained by the uneven distribution of regional compliance characterizing patients with lobar CT attenuations (compliant upper lobes and stiff lower lobes) contrasting with a more even distribution of regional compliances observed in patients with diffuse CT attenuations.¶Conclusions: In patients with ARDS, the cardiorespiratory effects of PEEP are affected by lung morphology rather than by the cause of the lung injury (primary versus secondary ARDS). The regional distribution of the loss of aeration and the type of atelectasis –“mechanical” with a massive loss of lung volume, or “inflammatory” with a preservation of lung volume – characterizing the lower lobes are the main determinants of the cardiorespiratory effects of PEEP.     

Experimental pulmonary Pneumocystis carinii infection in rabbits

Moderate to marked interstitial pneumonitis with many Pneumocystis organisms was found in rabbits treated with cortisone and antibiotics and instilled intranasally with a suspension of lung tissue from either a patient or a rabbit with this infection. Organisms and pulmonary lesions of similar severity and frequency were present in controls treated in the same manner but instilled with either saline or a boiled suspension of normal human lung tissue. The administration of antibiotics and infected rabbit lung suspension only produced less marked lung changes with fewer organisms. Rare organisms and minute foci of pneumonitis were encountered in normal rabbits which had received neither hormone, antibiotics, nor inoculum. The pulmonary lesions in the cortisone-treated rabbits resembled closely the findings in patients with the subclinical form of Pneumocystis pneumonitis. They did not reproduce the massive lesions of widespread Pneumocystis pneumonia in infants. The findings indicate that latent pulmonary Pneumocystis infection was widespread in these rabbits but do not establish the transmission of the disease. The activation of latent infection was dependent on an impairment of host resistance which in these experiments was produced most effectively by the administration of cortisone. The differences between the experimental lesions and those of typical Pneumocystis pneumonia in infants suggest that in man an unknown defect of host defenses other than that induced by prolonged hormone administration accounts for the increased susceptibility to the infection. It is concluded that in the presence of widespread latent Pneumocystis infection the development of active disease is a manifestation of altered host resistance.     

基于体素的COPD肺叶损伤及空间分布研究

目的 利用基于体素的定量CT，分析慢性阻塞性肺疾病(chronic obstructive pulmonary disease，COPD) 患者的肺叶损伤程度及空间分布特点。方法 在“数字肺”多研究中心中连续性纳入双气相扫描的COPD患者，测定小气道病变（functional small-airway disease, fSAD）和肺气肿（emphysema, Emph）的定量值；使用方差分析或秩和检验分析COPD各个肺叶之间肺气肿及小气道病变的肺叶损伤程度及肺叶分布差异；并进行各个肺叶的定量CT分布与肺功能的相关性分析。结果 最终纳入COPD患者50例。肺气肿及小气道病变均为右肺中叶损伤最重，其次是两肺上叶，而两肺下叶的损伤程度最轻；肺气肿及小气道病变均主要分布于左肺上叶，其次是右肺上叶，而右肺中叶的分布最少；两肺下叶的Emph和fSAD与FEV1%的相关性较好。结论 COPD患者肺叶的损伤程度以右肺中叶及两肺上叶为重，尤其是右肺中叶；对于病变的分布，肺气肿和小气道病变主要分布于左肺上叶，其次是右肺上叶；而两肺下叶对COPD患者肺功能的影响更大。     

Polarization-sensitive optical coherence tomography in end-stage lung diseases: an ex vivo pilot study

A non-invasive diagnostic tool to assess remodeling of the lung airways caused by disease is currently missing in the clinic. Measuring key features such as airway smooth muscle (ASM) thickness would increase the ability to improve diagnosis and enable treatment evaluation. In this research, polarization-sensitive optical coherence tomography (PS-OCT) has been used to image a total of 24 airways from two healthy lungs and four end-stage diseased lungs ex vivo, including fibrotic sarcoidosis, chronic obstructive pulmonary disease (COPD), fibrotic hypersensitivity pneumonitis, and cystic fibrosis. In the diseased lungs, except COPD, the amount of measured airway smooth muscle was increased. In COPD, airway smooth muscle could not be distinguished from surrounding collagen. COPD lungs showed increased alveolar size. 3D pullbacks in the same lumen provided reproducible assessment of airway smooth muscle (ASM). Image features such as thickened ASM and size/presence of alveoli were recognized in histology. The results of this study are preliminary and must be confirmed with further ex vivo and in vivo studies. PS-OCT is applicable for in vivo assessment of peribronchial and peribronchiolar lung structures and may become a valuable tool for diagnosis in pulmonology.     

Effect of Cardiopulmonary Bypass on Regional Antibiotic Penetration into Lung Tissue

The use of cardiopulmonary bypass (CPB) during cardiac surgery causes regional ventilation-perfusion mismatch, contributing to regional disturbances in antibiotic penetration into lung tissue. Ventilation-perfusion mismatch is associated with postoperative pneumonia, a frequent and devastating complication after cardiac surgery. In this prospective clinical animal study, we performed in vivo microdialysis to determine the effect of CPB on regional penetration of levofloxacin (LVX) into lung tissue. Six pigs underwent surgery with CPB (CPB group), and another six pigs underwent surgery without CPB (off-pump coronary artery bypass grafting; OPCAB group). LVX (750 mg) was administered intravenously to all pigs immediately after surgery. For regional measurements of LVX in pulmonary concentrations, microdialysis probes were inserted in both lungs of each pig. Pigs were placed in the right lateral position. Time versus concentration profiles of unbound LVX were measured in the upper and lower lung tissue and plasma in all pigs. In all pigs, maximum concentrations (C_max) of LVX were significantly lower in the upper lung than in the lower lung (OPCAB, P = 0.035; CPB, P < 0.001). Median C_max of LVX showed a significant difference in the upper versus lower lung in the CPB group (P < 0.05). No significant difference was found in the median C_max of LVX in the upper and the lower lung in the OPCAB group (P = 0.32). Our data indicate that CPB affects perioperative regional antibiotic penetration into lung tissue. Common clinical antibiotic dosing schemes should be reevaluated in patients undergoing coronary artery bypass grafting with CPB.     

Chronic colonization by Pseudomonas aeruginosa of patients with obstructive lung diseases: cystic fibrosis,bronchiectasis, and chronic obstructive pulmonary disease

Pseudomonas aeruginosa is isolated in sputum cultures from cystic fibrosis (CF) patients and adults with bronchiectasis (BS) and chronic obstructive pulmonary disease, but it is not well known if the characteristics of colonization in these latter patients are similar to those with CF. We examined 125 P. aeruginosa isolates obtained from 31 patients suffering from these diseases by pulsed field gel electrophoresis and genotyping of mucA and fpvA genes. The pattern of colonization, with dominance of a clonal strain and incidence of mucoid phenotypes, was similar in every group of patients; however, in some CF and BS patients, we detected the replacement or coexistence of 2 main clones. The main differences were found in the nucleotide position of less common mucA mutations, other than mucA22, and in the predominance of the different types of the pyoverdine receptor. Our results support a similar colonization pattern by P. aeruginosa in the different obstructive pulmonary diseases.     

Pneumocystis jirovecii pneumonia in non-HIV-infected patients in the era of novel immunosuppressive therapies

In human immunodeficiency virus (HIV)-infected patients, Pneumocystis jirovecii pneumonia (PCP) is a well-known opportunistic infection, and its management has been established. However, PCP is an emerging threat to immunocompromised patients without HIV infection, such as those receiving novel immunosuppressive therapeutics for malignancy, organ transplantation, or connective tissue diseases. Clinical manifestations of PCP are quite different between patients with and without HIV infections. In patients without HIV infection, PCP rapidly progresses, is difficult to diagnose correctly, and causes severe respiratory failure with a poor prognosis. High-resolution computed tomography findings are different between PCP patients with HIV infection and those without. These differences in clinical and radiologic features are the result of severe or dysregulated inflammatory responses that are evoked by a relatively small number of Pneumocystis organisms in patients without HIV infection. In recent years, the usefulness of PCR and serum β-d-glucan assay for rapid and noninvasive diagnosis of PCP has been revealed. Although corticosteroid adjunctive to anti-Pneumocystis agents has been shown to be beneficial in some populations, the optimal dose and duration remain to be determined. Recent investigations revealed that Pneumocystis colonization is prevalent, and that asymptomatic carriers are at risk for developing PCP and can serve as the reservoir for the spread of Pneumocystis by person-to-person transmission. These findings suggest the need for chemoprophylaxis in immunocompromised patients without HIV infection, although its indication and duration are still controversial. Because a variety of novel immunosuppressive therapeutics have been emerging in medical practice, further innovations in the diagnosis and treatment of PCP are needed.     

慢性阻塞性肺疾病患者与肺功能正常吸烟者CT肺实质灌注成像对照

目的 分析慢性阻塞性肺疾病（COPD）患者及肺功能正常吸烟者CT肺实质灌注图像的差异。方法 对63例COPD患者及20名肺功能正常吸烟者（对照组）行肺CTPI,将COPD患者分为轻度亚组（16例）、中度亚组（18例）、重度亚组（11例）和极重度亚组（18例）,在肺叶水平计算灌注缺损区与正常区CT值比值（R_HU）,比较各组体质量指数（BMI）、吸烟量及各肺叶R_HU的差异。结果 对照组BMI与重度、极重度COPD亚组比较,对照组吸烟量与极重度COPD亚组比较差异均有统计学意义（P=0.006、0.002、0.007）。同组各肺叶R_HU差异均无统计学意义（P均>0.05）。对照组右肺下叶R_HU与重度、极重度COPD亚组差异有统计学意义（P=0.03、0.02）,其他各肺叶R_HU各组差异均无统计学意义（P均>0.05）。对照组与各COPD亚组R_HU差异均有统计学意义（P均<0.05）;轻度与重度、与极重度COPD亚组,中度与极重度COPD亚组R_HU差异均有统计学意义（P=0.022、0.001、0.003）。结论 R_HU可区分COPD和肺功能正常吸烟者,有可能成为评估COPD严重程度的指标之一。     

HRCT定量观察慢性阻塞性肺疾病患者支气管重构

目的 观察不同临床表型慢性阻塞性肺疾病(COPD)患者肺段和亚段支气管重构的差异。 方法 COPD患者76例,正常对照者30名(正常组),均接受胸部HRCT检查。对双上肺尖后段及亚段、双下肺后基底段及亚段支气管进行定量分析,分别测量4支段和4支亚段支气管的壁厚度(WT)、腔内径(Din)、壁面积(WA)和壁面积百分比(WA%),比较组间各指标差异。 结果 76例COPD患者分为支气管炎型(A组,41例)和肺气肿型(B组,35例)2种临床表型。A组表现为支气管管壁增厚和管腔变窄,以亚段支气管明显;B组表现为肺密度减低和肺气肿,支气管壁增厚不明显或轻度增厚。A、B两组段和亚段支气管WT大于正常组(P<0.05),段支气管Din小于正常组,A组亚段支气管Din小于正常组,差异有统计学意义(P<0.01),A、B两组间差异也有统计学意义(P<0.05)。A组段和亚段支气管WA大于正常组(P<0.05)。A、B两组段和亚段支气管WA%大于正常组(P<0.05),亚段支气管WA%显著大于段支气管(P<0.05)。 结论 HRCT能够检测段和亚段支气管重构,有助于诊断COPD患者临床表型。     

The prevalence of airway obstruction among Japanese HIV-positive male patients compared with general population; a case–control study of single center analysis

Background and objectivePrevious studies have suggested that human immunodeficiency virus (HIV) infection and/or the airway colonization of Pneumocystis jirovecii (Pcj) impact on the progression of airway obstruction, such as chronic obstructive pulmonary disease (COPD). This study was aimed to evaluate the relationship between HIV infection, airway colonization of Pcj and airway obstruction in Japanese male patients.MethodsCase–control study of 49 HIV-positive and 257 HIV-negative men were enrolled in this study. Airway obstruction was determined by spirometry. Cigarette smoking was determined by a self report. Laboratory data were obtained from medical records. Among HIV positive patients, the airway colonization of Pcj was evaluated by induced sputum using the real time polymerase chain reaction method.ResultsForty-eight out of 49 (97.9%) HIV-positive patients received antiretroviral therapy, and their median CD4 cell counts were 491/μL (79–935). The prevalence of airway obstruction as determined by spirometry was 10.2% (5/49) in HIV-positive subjects and 2.4% (5/208) in HIV-negative subjects (p = 0.024). Compared with the control group, HIV-positive patients were significantly younger (median age 44 vs 40, p = 0.019). After adjusting for age, pack-years of smoking, HIV infection was an independent risk factor for airway obstruction (OR; 10.93, 95%CI 1.99–60.1, p = 0.006). None of patient was detected the airway colonization of Pcj.ConclusionsHIV infection was an independent risk factor for airway obstruction regardless of airway colonization of Pcj. Health-care providers should be aware of the increased likelihood of airway obstruction among HIV-positive patients.     

Comparison of 133Xenon radiospirometry with quantitative 99mTecnnetium-macroaggregated albiimin perfusion scintigraphy

Summary. Radiospirometry with ¹³³Xenon and perfusion scintigraphy with ^99mTech-netium-labelled macroaggregated albumin were compared in 22 patients with lung diseases scheduled for surgery. The tracers were given intravenously and, with a gamma camera coupled to a computer, regional lung function was obtained from the count rate in the upper and lower halves of the lungs. There were no significant differences in regional lung function as estimated from the ^99mTc perfusion scintigraphy and from the ¹³³Xe method taking perfusion as well as ventilation into account. When the initial ^lMXe distribution alone was employed, the regional perfusion was underestimated in the right lower lung region and overestimated in the left lung. This is probably due to difficulties in placing the regions of interest. When a gamma camera is used, perfusion scintigraphy with “Technetium macro-aggregated albumin is easy to perform aad has good counting statistics. This method is therefore advocated for the pre-operative assessment of regional lung function.     

Regional distribution of pulmonary ventilation and perfusion in elderly subjects

Using radioactive xenon, we measured the regional distribution of pulmonary ventilation and blood flow in six normal men, whose ages ranged between 65 and 75 yr. The measurements were made in the standing position. The static volume-pressure relation of the lungs was also measured in five of the subjects. The results indicate that by comparison with normal young men: (a) Blood flow to the upper lung zones was increased, although it still remained predominant in the lower zones. (b) Ventilation distribution during a vital capacity inspiration was similar to that seen in young subjects. (c) In five of the six elderly subjects, however, the distribution of ventilation in the resting tidal volume range was not preferential to the lower zones as it was in young men. This was probably caused by airway closure in the lower lung zones. The elderly subjects thus exhibit during normal tidal volume breathing a ventilation distribution pattern similar to that observed in young subjects when breathing at low lung volumes, i.e., near residual volume. This difference is probably due to the combined effect of the loss in elastic recoil of the lungs observed in the elderly subjects and of a decreased resistance to collapse of the aged airways. These findings suggest that in the elderly subjects there is a significant regional ventilation-perfusion impairment during quiet breathing, which may explain in part the reported increase in alveolar-arterial oxygen difference with advancing age.     

An Ultrasound Surface Wave Technique for Assessing Skin and Lung Diseases

Systemic sclerosis (SSc) is a multi-organ connective tissue disease characterized by immune dysregulation and organ fibrosis. Severe organ involvement, especially of the skin and lung, is the cause of morbidity and mortality in SSc. Interstitial lung disease (ILD) includes multiple lung disorders in which the lung tissue is fibrotic and stiffened. The purpose of this study was to translate ultrasound surface wave elastography (USWE) for assessing patients with SSc and/or ILD via measuring surface wave speeds of both skin and superficial lung tissue. Forty-one patients with both SSc and ILD and 30 healthy patients were enrolled in this study. An external harmonic vibration was used to generate the wave propagation on the skin or lung. Three excitation frequencies of 100, 150 and 200?Hz were used. An ultrasound probe was used to measure the wave propagation in the tissue non-invasively. Surface wave speeds were measured on the forearm and upper arm of both left and right arm, as well as the upper and lower lungs, through six intercostal spaces of patients and healthy patients. Viscoelasticity of the skin was calculated by the wave speed dispersion with frequency using the Voigt model. The magnitudes of surface wave speed and viscoelasticity of patients' skin were significantly higher than those of healthy patients (p?<0.0001) for each location and each frequency. The surface wave speeds of patients' lung were significantly higher than those of healthy patients (p?<0.0001) for each location and each frequency. USWE is a non-invasive and non-ionizing technique for measuring both skin and lung surface wave speed and may be useful for quantitative assessment of SSc and/or ILD.     

Serum (1 → 3) β-d-glucan assay for discrimination between Pneumocystis jirovecii pneumonia and colonization

Polymerase chain reaction (PCR) technique is being increasingly used for the microbiological diagnosis of Pneumocystis pneumonia (PCP). As PCR is highly sensitive, it can be positive even in a patient with Pneumocystis colonization. In this study, we evaluated whether the β-d-glucan assay could be used to differentiate between PCP and Pneumocystis jirovecii colonization in immunocompromised patients with pulmonary infiltrates. We retrospectively evaluated data from 166 consecutive patients who underwent bronchoalveolar lavage for the diagnosis of PCP. Serum levels of β-d-glucan in the negative, colonization, probable PCP, and definite PCP groups were 20.2 ± 6.3, 48.8 ± 15.9, 89.9 ± 20.2, 224.9 ± 25.9 pg/mL, respectively. The β-d-glucan levels in the definite PCP group were significantly higher than those in the other 3 groups (p < 0.001). Serum β-d-glucan levels in patients with either definite or probable PCP (173.1 ± 18.8 pg/mL) were significantly greater than those in patients with colonization who had positive PCR results but improved without anti-PCP treatment (p < 0.002). The cut-off level for discrimination was estimated to be 33.5 pg/mL, with which the positive predictive value was 0.925. These results indicate that β-d-glucan is a useful marker to differentiate between PCP and Pneumocystis colonization. A positive β-d-glucan assay result might be a good indication to begin anti-PCP treatment.     

Temporal changes in resistance mechanisms in colonizing Escherichia coli isolates with reduced susceptibility to fluoroquinolones

The objective of this study was to characterize the temporal variability of fluoroquinolone resistance mechanisms among Escherichia coli colonizing the gastrointestinal tract of hospitalized patients. Patients with new fluoroquinolone-resistant E. coli (FQREC) colonization were followed with serial fecal sampling until discharge or death. Genetic mechanism(s) of resistance for all FQREC isolates was characterized, including mutations in gyrA and parC and efflux pump overexpression. Of 451 subjects, 73 (16.2%) became newly colonized with FQREC. There was significant variability in regard to temporal changes in resistance mechanisms and levofloxacin MICs among isolates from individual patients. Compared to patients with transient colonization, patients with persistent colonization were more likely to have a urinary catheter (P = 0.04), diarrhea (P = 0.04), and a longer duration of hospitalization (22 and 9.0 mean days, respectively; P = 0.01) prior to sampling. Our data demonstrate the significant variability of resistance mechanisms in colonizing E. coli isolates among hospitalized patients.     

PPARγ in emphysema: blunts the damage and triggers repair?

Cigarette smoke is the most common cause of pulmonary emphysema, which results in an irreversible loss of lung structure and function. Th1 and Th17 immune responses have been implicated in emphysema pathogenesis; however, the drivers of emphysema-associated immune dysfunction are not fully understood. In this issue of the JCI, Shan and colleagues found that peroxisome proliferator–activated receptor γ (PPARγ) is downregulated in APCs isolated from the lungs of emphysematous chronic smokers and mice exposed to cigarette smoke. Furthermore, treatment with a PPARγ agonist prevented emphysema development and appeared to reduce emphysema-associated lung volume expansion in mice exposed to cigarette smoke. Further work will need to be done to evaluate the potential of PPARγ agonists to restore lung capacity in emphysematous patients. Pulmonary emphysema is a major component of chronic obstructive pulmonary disease (COPD) and involves the loss of alveolar units distal to the terminal bronchioles. Even though COPD holds an unenviable position as the world’s fourth-leading cause of death, current medical interventions have little to offer beyond symptomatic relief. Meanwhile, the prevalence of COPD is expected to continue to rise as low- and middle-income countries join in the developed world’s tobacco addiction. If we are to avoid this grim projection, we must expand our knowledge of the basic mechanisms behind lung injury and repair before translating these findings into novel therapeutic treatments.     

Sequential changes of Legionella antigens and bacterial load in the lungs and urines of a mouse model of pneumonia

Legionella pneumophila is an important cause of community- and hospital-acquired pneumonia. In spite of the introduction of the urinary antigen detection method, Legionella pneumonia may be still underdiagnosed. We performed kinetic and quantitative analysis of diagnostic markers, such as bacterial loads, DNA assays, and antigen titers, in a 28-day time course murine model of L. pneumophila pneumonia. L. pneumophila replicated approximately 100-fold in the lungs of A/J mice in the first 48 h, and then became undetectable on day 14. Unexpectedly, pathogens other than L. pneumophila were consistently recovered from the lungs and livers at the acute phases, although those numbers were far below Legionella loads in the lungs. The peaks of specific antigen titer were observed on 48 h in the lungs, bronchoalveolar lavage (BAL) fluids, and urines and sustained positive even at 28 days after the infection. Especially, the lung homogenates and BAL fluids demonstrated 16 to 64 times higher levels of antigen titer than the urines by the end of observation. Legionella-specific DNA in the lungs was detected by polymerase chain reaction and loop-mediated isothermal amplification methods until 7 and 14 days after the infection, respectively. The inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin 6, and MIP-2, exhibited a peak on the acute phase, whereas the maximal production of high mobility group box 1 in the serum was observed on day 7. These results characterized the kinetic nature of diagnostic markers in L. pneumophila pneumonia. The present data suggested prolonged and compartmentalized deposition of antigen in the lungs, which may have an impact on the diagnosis of L. pneumophila pneumonia, especially in missed cases even after recovery from disease.