A randomized controlled trial of vitamin E and selenium on rate of decline in lung function

Background

The intake of nutrients with antioxidant properties is hypothesized to augment antioxidant defenses, decrease oxidant damage to tissues, and attenuate age-related rate of decline in lung function. The objective was to determine whether long-term intervention with selenium and/or vitamin E supplements attenuates the annual rate of decline in lung function, particularly in cigarette smokers.

Methods

The Respiratory Ancillary Study (RAS) tested the single and joint effects of selenium (200 μg/d L-selenomethionine) and vitamin E (400 IU/day all rac-α-tocopheryl acetate) in a randomized double-blind placebo-controlled trial. At the end of the intervention, 1,641 men had repeated pulmonary function tests separated by an average of 3 years. Linear mixed-effects regression models estimated the effect of intervention on annual rate of decline in lung function.

Results

Compared to placebo, intervention had no main effect on either forced expiratory volume in the first second (FEV₁) or forced expiratory flow (FEF_25–75). There was no evidence for a smoking by treatment interaction for FEV₁, but selenium attenuated rate of decline in FEF_25–75 in current smokers (P = 0.0219). For current smokers randomized to selenium, annual rate of decline in FEF_25–75 was similar to the annual decline experienced by never smokers randomized to placebo, with consistent effects for selenium alone and combined with vitamin E.

Conclusions

Among all men, there was no effect of selenium and/or vitamin E supplementation on rate of lung function decline. However, current smokers randomized to selenium had an attenuated rate of decline in FEF_25–75, a marker of airflow.

Trial registration

Clinicaltrials.gov identifier: NCT00241865.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-015-0195-5) contains supplementary material, which is available to authorized users.     

血清sTREM-1、肺功能指数与肺癌患者术后肺部感染的关系及其预测价值研究

目的:探讨血清髓样细胞触发受体-1(sTREM-1)、肺功能指数与肺癌患者术后肺部感染的关系及其预测价值。方法:回顾性分析2016年1月-2019年1月在我院进行手术治疗的115例肺癌患者的临床资料,根据患者术后72 h是否发生肺部感染将其分为感染组(n=28)及未感染组(n=87)。对比两组患者临床资料、术后6 h血清s TREM-1、降钙素原(PCT)水平及术前肺功能指数[第一秒用力呼气量(FEV1)、呼气流量峰值(PEF)]变化,记录感染组患者痰细菌培养结果,采用Logistic分析肺癌患者术后感染的影响因素,并采用受试者工作特征(ROC)曲线分析s TREM-1、FEV1、PEF在肺癌术后感染的预测价值。结果:感染组术后入住ICU比例大于未感染组,感染组TNM分期为IV期的比例大于未感染组(P0.05),感染组术后6 h血清s TREM-1、PCT水平高于未感染组,术前FEV1、PEF水平低于未感染组(P0.05)。感染组痰培养结果提示G-菌为17例,占60.71%;G+菌10例,占35.71%;真菌1例,占3.57%。二元多因素Logistic分析提示术后6 h血清s TREM-1水平升高、术前FEV1下降及PEF下降、术后入住ICU为肺癌患者术后感染的独立影响因素。三者联合预测曲线下面积为0.850(95%CI:1.350～1.745,P=0.000),敏感度与特异性分别为91.3%与80.6%,优于s TREM-1、FEV1、PEF的单独预测效能。结论:s TREM-1水平升高,术前FEV1、PEF水平降低与肺癌患者术后肺部感染密切相关,对s TREM-1、FEV1、PEF三者联合分析对于预测肺癌患者术后肺部感染的发生具有较高的预测价值。     

Epidemiology,genetics, and subtyping of preserved ratio impaired spirometry (PRISm) in COPDGene

Background

Preserved Ratio Impaired Spirometry (PRISm), defined as a reduced FEV₁ in the setting of a preserved FEV₁/FVC ratio, is highly prevalent and is associated with increased respiratory symptoms, systemic inflammation, and mortality. Studies investigating quantitative chest tomographic features, genetic associations, and subtypes in PRISm subjects have not been reported.

Methods

Data from current and former smokers enrolled in COPDGene (n = 10,192), an observational, cross-sectional study which recruited subjects aged 45–80 with ≥10 pack years of smoking, were analyzed. To identify epidemiological and radiographic predictors of PRISm, we performed univariate and multivariate analyses comparing PRISm subjects both to control subjects with normal spirometry and to subjects with COPD. To investigate common genetic predictors of PRISm, we performed a genome-wide association study (GWAS). To explore potential subgroups within PRISm, we performed unsupervised k-means clustering.

Results

The prevalence of PRISm in COPDGene is 12.3%. Increased dyspnea, reduced 6-minute walk distance, increased percent emphysema and decreased total lung capacity, as well as increased segmental bronchial wall area percentage were significant predictors (p-value <0.05) of PRISm status when compared to control subjects in multivariate models. Although no common genetic variants were identified on GWAS testing, a significant association with Klinefelter’s syndrome (47XXY) was observed (p-value < 0.001). Subgroups identified through k-means clustering include a putative “COPD-subtype”, “Restrictive-subtype”, and a highly symptomatic “Metabolic-subtype”.

Conclusions

PRISm subjects are clinically and genetically heterogeneous. Future investigations into the pathophysiological mechanisms behind and potential treatment options for subgroups within PRISm are warranted.

Trial registration

Clinicaltrials.gov Identifier: NCT000608764.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-014-0089-y) contains supplementary material, which is available to authorized users.     

纤维化性间质性肺疾病抗纤维化治疗的单中心真实世界研究

摘要 目的：分析真实世界中纤维化性间质性肺疾病（FILD）患者经抗纤维化治疗后的疗效及安全性,疾病进展的风险因素。方法：纳入首次诊断为FILD且开始口服吡非尼酮或尼达尼布抗纤维化治疗的患者。随访2年,收集患者的临床资料,分析其基线特征,包括性别、年龄、吸烟史、基础肺功能[用力肺活量（FVC）、一氧化碳弥散量(DLCO)],合并症及共用药物等。记录患者抗纤维化起始时、抗纤维化治疗12个月、24个月3个时间点的肺功能,分析FVC及DLCO的年下降率。收集药物相关的不良反应及耐受情况。建立Logistic回归模型分析临床变量与疾病进展的关系。结果：167例FILD患者经抗纤维化治疗12个月后,FVC及DLCO与治疗前相比均无统计学差异(P>0.05)。67例FILD患者经抗纤维化治疗24月后FVC及DLCO相较治疗前分别下降,但无统计学差异(P>0.05)。110名接受吡非尼酮治疗的患者出现98例不良事件,57名接受尼达尼布治疗的患者共出现70例不良事件,仅部分不良事件导致停药。两种抗纤维化药物最常见的副作用都是腹泻。与吡非尼酮相比,尼达尼布因不良事件导致的停药率明显更高（P<0.05）。Logistic回归分析显示抗纤维化治疗后12月内疾病进展的风险因素为吸烟、特发性肺纤维化（IPF）患者,而DLCO是疾病进展的保护因素。结论：真实世界中抗纤维化治疗可维持FILD患者FVC及DLCO稳定,抗纤维化药物相关不良反应均可耐受,安全性较高。吸烟及IPF患者更容易出现疾病进展,较高的DLCO是FILD患者疾病进展的保护因素。     

慢性阻塞性肺疾病患者超声监测膈肌增厚率与肺功能的相关性

摘要 目的：探讨慢性阻塞性肺疾病(Chronic obstructive pulmonary disease,COPD)患者超声监测膈肌增厚率与肺功能的相关性。方法：2019年1月到2020年12月选择在本院诊治的COPD患者72例作为COPD组,同期选择在本院体检的健康人72例作为对照组。采用超声监测两组入选者的膈肌增厚率,使用肺功能测定仪测定呼气流量峰值(peak expiratory flow,PEF)、第1 秒用力呼气容积占预计值百分比(Forced Expiratory Volume in the first second,FEV₁)、肺活量25 %时用力呼气流速(Vmax25%,V25)、肺活量50 %时用力呼气流速(Vmax50%,V50)、肺活量75 %时用力呼气流速(Vmax75%,V75)等指标并进行相关性分析。结果：COPD组的膈肌增厚率低于对照组,对比差异有统计学意义(P<0.05)。COPD组的FEV₁、PEF、V25、V50、V75值都低于对照组,对比差异都有统计学意义(P<0.05)。在COPD组患者中,Pearson相关分析显示膈肌增厚率与FEV₁、PEF、V25、V50、V75都存在正相关性(P<0.05)。Logistic回归分析显示FEV₁、PEF、V25、V50、V75为影响膈肌增厚率的重要影响因素P<0.05)。结论：COPD患者超声监测可显示膈肌增厚率与肺功能降低,两者存在相关性,肺功能下降也是导致患者膈肌增厚率降低的重要危险因素。     

间质性肺疾病患者生活质量与肺功能和焦虑抑郁情绪的关系及其影响因素分析

摘要 目的：探讨间质性肺疾病（ILD）患者生活质量与肺功能和焦虑抑郁情绪的关系及其影响因素。方法：选取2019年3月至2020年10月期间我院收治的100例ILD患者。比较ILD患者与一般人群的圣乔治呼吸问卷（SGRQ）评分、肺功能指标[第1秒用力呼气容积（FEV₁）、用力肺活量（FVC）、肺总量（TLC）及一氧化碳弥散量（DLCo）];观察患者的医院焦虑抑郁量表（HADS）评分（该评分包括焦虑和抑郁评分两部分）;分析ILD患者的SGRQ评分与肺功能指标,焦虑、抑郁评分的相关性;单因素、多因素Logistic回归分析ILD患者生活质量的影响因素。结果：ILD患者的SGRQ各维度评分及总分均高于一般人群,FVC、FEV₁、TLC及DLCo均低于一般人群（P<0.05）;ILD患者焦虑评分和抑郁评分均较高;ILD患者SGRQ各维度评分均与FVC、FEV1、TLC和DLCo呈负相关（P<0.05）,均与焦虑评分和抑郁评分呈正相关（P<0.05）。单因素分析结果显示,不同年龄、是否吸烟、不同收入情况的ILD患者生活质量有差异（P<0.05）;多因素Logistic回归分析结果显示DLCo、FVC、焦虑和抑郁情绪是ILD患者生活质量的影响因素（P<0.05）,其中焦虑情绪对其生活质量的影响最为显著。结论：ILD患者的生活质量与肺功能和焦虑抑郁情绪有关,提示临床工作中可通过干预ILD患者肺功能和焦虑抑郁情绪以改善其生活质量。     

Pulmonary function of a firemen-diver population: a longitudinal study

Non smoking, male professional firemen-divers (n = 20) underwent two pulmonary function tests (PFT) separated by 8–9 years. Measured data were compared to European Coal Steel Community recommended reference values to permit cross-sectional and then longitudinal studies. Higher vital capacity (VC) and forced expiratory volume in 1 s (FEV₁; bothP<0.001), and lower residual volume (P<0.01) were observed in both PFT. Longitudinal analysis showed a smaller VC reduction than FEV₁ reduction, leading to a FEV₁/VC percentage decrease with time. Maximal mid expiratory flow (MMEF) and MMEF/VC changes during this 9-year period showed an unusually pronounced decrease, suggesting possible chronic effects of diving on small airways. Thus, it is suggested from our observations that a hyperbaric stimulus compensates in part for the effects of aging on VC and that obstructive disease could occur in subjects with long diving experience.     

肺腺癌发生阻塞性肺炎的临床分析

目的研究阻塞性肺炎与肺腺癌发病的关系以及对预后的影响。方法对2003年12月至2013年1月于大连医科大学附属二院确诊的436例肺腺癌患者病历进行回顾,根据患者临床特征进行分组,并进行统计学分析。结果晚期肺腺癌患者更易出现阻塞性肺炎（χ2=5．662,P=0．017）;中心型肺腺癌较周围型更易出现阻塞性肺炎（χ2=4．432,P=0．035）;在肺腺癌中,性别、年龄、吸烟史以及体重下降与否与阻塞性肺炎的发生经比较差异无统计学意义（P〉0．05）。结论阻塞性肺炎的发生与晚期肺腺癌以及中心型肺腺癌有关,重视筛查对肺腺癌的诊断和预后有重要意义。     

Change in serum KL-6 level from baseline is useful for predicting life-threatening EGFR-TKIs induced interstitial lung disease

Background

A high incidence of interstitial lung disease (ILD) has been reported in patients with advanced non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), particularly in Japanese populations. A previous report from our laboratory demonstrated that KL-6 was a useful serum biomarker to assess the severity of drug-induced pneumonitis. Based on these observations, this study was conducted to evaluate the risk factors of EGFR-TKIs induced ILD and the usefulness of monitoring serum KL-6 levels in patients who developed EGFR-TKIs induced ILD in a large multi-institutional setting.

Methods

We retrospectively reviewed clinical records and radiographies of 341 patients with advanced NSCLCs who were treated with EGFR-TKIs, and analyzed risk factors for the development of EGFR-TKIs induced ILD. Changes of circulating levels of KL-6 were also evaluated in the patients who developed EGFR-TKIs induced ILD.

Results

Among the 341 patients included in this study, 20 (5.9%) developed EGFR-TKIs induced ILD, and 9 (2.6%) died from ILD. Univariate analyses revealed that only preexisting pulmonary fibrosis was a significant risk factor for the development of EGFR-TKIs induced ILD (p = 0.003). Absolute levels of circulating KL-6 at neither baseline nor the onset of ILD could discriminate between life-threatening and non-life threatening EGFR-TKIs induced ILDs. However, we found that the ratios of serum KL-6 levels just after the onset of EGFR-TKIs induced ILD to those at baseline could quite precisely distinguish survivors from non-survivors (p = 0.006) as well as acute interstitial pneumonia (AIP) pattern from non-AIP pattern (p = 0.005).

Conclusions

The results of this study strongly support the potential of KL-6 as a diagnostic biomarker for life-threatening EGFR-TKIs induced ILD. Monitoring of KL-6 is also useful to evaluate the progression and severity of EGFR-TKIs induced ILD.     

Paired inspiratory-expiratory chest CT scans to assess for small airways disease in COPD

Background

Gas trapping quantified on chest CT scans has been proposed as a surrogate for small airway disease in COPD. We sought to determine if measurements using paired inspiratory and expiratory CT scans may be better able to separate gas trapping due to emphysema from gas trapping due to small airway disease.

Methods

Smokers with and without COPD from the COPDGene Study underwent inspiratory and expiratory chest CT scans. Emphysema was quantified by the percent of lung with attenuation < −950HU on inspiratory CT. Four gas trapping measures were defined: (1) Exp₋₈₅₆, the percent of lung < −856HU on expiratory imaging; (2) E/I MLA, the ratio of expiratory to inspiratory mean lung attenuation; (3) RVC_856-950, the difference between expiratory and inspiratory lung volumes with attenuation between −856 and −950 HU; and (4) Residuals from the regression of Exp₋₈₅₆ on percent emphysema.

Results

In 8517 subjects with complete data, Exp₋₈₅₆ was highly correlated with emphysema. The measures based on paired inspiratory and expiratory CT scans were less strongly correlated with emphysema. Exp₋₈₅₆, E/I MLA and RVC_856-950 were predictive of spirometry, exercise capacity and quality of life in all subjects and in subjects without emphysema. In subjects with severe emphysema, E/I MLA and RVC_856-950 showed the highest correlations with clinical variables.

Conclusions

Quantitative measures based on paired inspiratory and expiratory chest CT scans can be used as markers of small airway disease in smokers with and without COPD, but this will require that future studies acquire both inspiratory and expiratory CT scans.     

单光子发射计算机断层扫描肺灌注显像(SPECT/CT)在肺恶性肿瘤放疗中的应用进展

放射性肺损伤是肺恶性肿瘤放疗后常见的并发症,其限制肺恶性肿瘤的放疗剂量并影响总体疗效及患者生存质量。本文复习放射性肺损伤发生机制及影响因素,分析剂量体积直方图、肺功能测定、TGF-β1等临床常用放射性肺损伤评估指标的利弊。参考近年文献,总结了单光子发射计算机断层扫描肺灌注显像(SPECT/CT)在肺恶性肿瘤放疗中的应用,从其原理、区域肺功能的显像、对放疗的评估与指导应用几方面阐述。认为SPECT/CT能实时反映区域肺功能、肺功能改变以及其解剖定位,可在放疗中起监测作用,对准确评估肺功能、预测放疗后肺损伤,优化放疗计划有重要价值。SPECT/CT肺灌注显像还需要多中心、大样本、长时间随访资料进一步深入研究。     

阿托伐他汀治疗慢性阻塞性肺疾病改善肺功能的临床效果分析

目的:探讨阿托伐他汀对改善慢性阻塞性肺疾病肺功能的临床效果。方法:60例C0PD患者随机分为对照组组和治疗组各30例,对照组给予常规治疗,治疗组在对照组的基础上口服阿托伐他汀(20mg/d)。两组患者随访12周,比较分析两组患者肺功能改善情况及生活质量的变化情况。结果:两组治疗前肺功能无明显差异,治疗后两组肺功能较治疗前均有显著改善。治疗组较对照组第1秒用力呼气容积(FEVl)、用力肺活量(Fvc)、FEVl/FVC和FEVI占预计值百分比(FEVl%Pred)等明显改善,差异有显著的统计学意义(P<0.01);并且生活质量评分治疗组明显高于对照组,差异有显著的统计学意义(P<0.01)。结论:阿托伐他汀能明显提高慢性阻塞性肺疾病的肺功能,提高患者的生活质量。     

Differential proteome profiling of pleural effusions from lung cancer and benign inflammatory disease patients

The pleural effusion proteome has been found containing information that directly reflects pathophysiological status and represents a potential diagnostic value for pulmonary diseases. However, the variability in protein composition between malignant and benign effusions is not well understood. Herein, we investigated the changes of proteins in pleural effusions from lung adenocarcinoma and benign inflammatory disease (pneumonia and tuberculosis) patients by two-dimensional difference gel electrophoresis (2D-DIGE). Twenty-eight protein spots displayed significantly different expression levels were positively identified by MALDI-TOF-MS representing 16 unique proteins. Five identified protein candidates were further validated and analyzed in effusions, sera or tissues. Among them, hemopexin, fibrinogen gamma and transthyretin (TTR) were up-regulated in cancer samples. The effusion concentration of serum amyloid P component (SAP) was significantly lower in lung cancer patients than in benign inflammatory patients, but no differences were found in sera samples. Moreover, a Jumonji C (JmjC)-domain-containing protein, JMJD5, was observed to be down-regulated in malignant effusions, lung cancer tissues and cancer cells. These results shed light on the altered pleural effusion proteins as a useful and important complement to plasma or other routine clinical tests for pulmonary disease diagnosis.     

Inhibition of HMGCoA reductase by simvastatin protects mice from injurious mechanical ventilation

Background

Mortality from severe acute respiratory distress syndrome exceeds 40% and there is no available pharmacologic treatment. Mechanical ventilation contributes to lung dysfunction and mortality by causing ventilator-induced lung injury. We explored the utility of simvastatin in a mouse model of severe ventilator-induced lung injury.

Methods

Male C57BL6 mice (n = 7/group) were pretreated with simvastatin or saline and received protective (8 mL/kg) or injurious (25 mL/kg) ventilation for four hours. Three doses of simvastatin (20 mg/kg) or saline were injected intraperitoneally on days −2, −1 and 0 of the experiment. Lung mechanics, (respiratory system elastance, tissue damping and airway resistance), were evaluated by forced oscillation technique, while respiratory system compliance was measured with quasi-static pressure-volume curves. A pathologist blinded to treatment allocation scored hematoxylin-eosin-stained lung sections for the presence of lung injury. Pulmonary endothelial dysfunction was ascertained by bronchoalveolar lavage protein content and lung tissue expression of endothelial junctional protein Vascular Endothelial cadherin by immunoblotting. To assess the inflammatory response in the lung, we determined bronchoalveolar lavage fluid total cell content and neutrophil fraction by microscopy and staining in addition to Matrix-Metalloprotease-9 by ELISA. For the systemic response, we obtained plasma levels of Tumor Necrosis Factor-α, Interleukin-6 and Matrix-Metalloprotease-9 by ELISA. Statistical hypothesis testing was undertaken using one-way analysis of variance and Tukey’s post hoc tests.

Results

Ventilation with high tidal volume (HVt) resulted in significantly increased lung elastance by 3-fold and decreased lung compliance by 45% compared to low tidal volume (LVt) but simvastatin abrogated lung mechanical alterations of HVt. Histologic lung injury score increased four-fold by HVt but not in simvastatin-pretreated mice. Lavage pleocytosis and neutrophilia were induced by HVt but were significantly attenuated by simvastatin. Microvascular protein permeability increase 20-fold by injurious ventilation but only 4-fold with simvastatin. There was a 3-fold increase in plasma Tumor Necrosis Factor-α, a 7-fold increase in plasma Interleukin-6 and a 20-fold increase in lavage fluid Matrix-Metalloprotease-9 by HVt but simvastatin reduced these levels to control. Lung tissue vascular endothelial cadherin expression was significantly reduced by injurious ventilation but remained preserved by simvastatin.

Conclusion

High-dose simvastatin prevents experimental hyperinflation lung injury by angioprotective and anti-inflammatory effects.     

COPD患者改善体质量指数与肺功能变化的相关性

目的:探讨COPD患者改善体质量指数(BMD与肺功能变化的相关性.方法:经加强营养达正常BMI的患者(A组)与低BMI的COPD患者(B组),比较2组肺功能指标、6min步行距离、呼吸困难评分.结果:与B组相比,A组FEV1％、FEV1/FVC、SVC、MVV、IC均明显升高(P＜0.01),RV/TLC明显上升(P＜0.01),6min步行距离延长(P＜0.01)、呼吸困难评分明显降低(P＜0.01).Pearson 相关性分析显示,FEV1％、FEV1/FVC、SVC、MVV、IC、RV/TIC与BMI相关,6min步行距离与BMI呈正相关,呼吸困难评分与BMI呈负相关.结论:改善BMI可明显改善COPD患者的肺功能指标,减轻临床症状.     

一种猪模型的体外肺灌注系统的建立

目的:体外肺灌注技术(Ex vivo lung perfusion, EVLP)对于肺移植的实施意义重大,但成本昂贵。本文采用国产经济材料建立猪模型的EVLP系统,以探索保证系统性能的同时降低移植费用。方法:我们首先依据国产材料配置肺灌注液,并组装管道、连接仪器以建立EVLP系统;之后通过外科手段获得3头家猪的肺脏,并灌注肺灌注液,低温保存6小时;最后我们将肺脏连接到EVLP系统,通过血气分析和肺功能检查来评估肺脏随时间变化的状况。结果:离体并在低温保存6小时的猪肺脏,通过我们建立的相对经济的EVLP系统,可以在2小时内维持良好的氧合功能和肺生理指标:肺动脉压、气道峰压、平台压力、肺动脉氧气分压和二氧化碳分压和左心房的氧气分压和二氧化碳分压都保持稳定,同时肺脏具有正常的颜色和弹性,没有明显水肿和功能损害。结论:我们建立的EVLP系统可以有效地维护离体猪肺的生理功能,且降低了成本,从而为肺移植体外肺灌注技术的优化应用提供了研究基础。     

Effects of some indoor environmental factors on respiratory symptoms and lung function in a sample of young non smokers in North Italy

Summary We evaluated the effects of some indoor environmental factors in a non smoking subsample (n=381, age 8–19 years) of the general population living in the Po River Delta. Each subject completed an interviewer-administered standardized questionnaire on respiratory symptoms and risk factors. Acceptable maneuvers of forced vital capacity and slope of alveolar plateau of nitrogen were obtained in 96% and 59% of the subjects, respectively. In the houses there were more frequently natural gas for cooking (86%) than bottled gas (14%) and central heating (82%) than stove (18%). As regards passive smoking exposure, 18% of subjects had both parents smoking, 50% had one parent smoking. Significantly higher prevalence rates of wheeze, dyspnea, diagnosis of asthma were found in subjects of both sexes using bottled gas for cooking in comparison to those using natural gas, when also exposed to passive smoking. An insignificant trend towards higher symptom rates was shown by those using stove, instead of central heating. Lung function was affected only in females: those with both parents smoking had reduced forced expirograms, those with bottled gas for cooking or stove for heating had a decreased peak expiratory flow. Interactions of stove and passive smoking on peak expiratory flow and on slope of alveolar plateau were statistically significant. These findings confirm the mild adverse respiratory effects of certain home environment factors shown by other epidemiologic surveys in North Europe and in the USA. They have been a basis for the implementation, under the auspices of National Research Council and Electric Energy Authority, of future specific studies in which continuous monitoring of indoor pollutants and repeated recording of symptoms and lung function in North and Central Italy will be performed.