•Controversy exists about the pathogenesis of IPF-AEs.•Early in the development of an IPF-AE, IL-6 and IL-8 blood levels are significantly increased.•While TGF-β, IL-4, IL-10, and IL-13 levels show ...no difference compared stable IPF patients.•Increased IL-6 and IL-8 levels are related to a higher risk of death in all IPF patients.•Further studies are necessary to clarify the enigma of IPF-AEs etiopathogenesis.
Controversy exists about the pathogenesis of idiopathic pulmonary fibrosis acute exacerbations (IPF-AEs). According to one hypothesis IPF-AEs represent the development of any etiology diffuse alveolar damage (DAD) upon usual interstitial pneumonia (UIP), whilst other researchers argue that an accelerated phase of the intrinsic fibrotic process of unknown etiology prevails, leading to ARDS. Different cytokines might be involved in both processes. The aim of this study was to assess pro-inflammatory and pro-fibrotic cytokines in the peripheral blood from stable and exacerbated IPF patients.
Consecutive IPF patients referred to our department were included. Diagnoses of IPF and IPF-AE were based on international guidelines and consensus criteria. The interleukins (IL)-4, IL-6, IL-8, IL-10, and IL-13 as well asactive transforming growth factor-beta (TGF-β) were measured in blood from both stable and exacerbated patients on the day of hospital admission for deterioration. Subjects were followed for 12months. Mann-Whitney test as well as Tobit and logistic regression analyses were applied.
Among the 41 patients studied, 23 were stable, and 18 under exacerbation; of the latter, 12 patients survived. The IL-6 and IL-8 levels were significantly higher in exacerbated patients (p=0.002 and p=0.046, respectively). An increase in either IL-6 or IL-8 by 1pg/ml increases the odds of death by 5.6% (p=0.021) and 6.7% (p=0.013), respectively, in all patients. No differences were detected for the other cytokines.
High levels of IL-6 and IL-8 characterize early-on IPF-AEs and an increase in the levels of IL-6 and IL-8 associates with worse outcome in all patients. However, as the most representative pro-fibrotic cytokines, TGF-β, IL-10, IL-4 and IL-13 were not increased and given the dualistic nature, both pro-inflammatory and pro-fibrotic of IL-6 further studies are necessary to clarify the enigma of IPF-AEs etiopathogenesis.
Abstract
Background
Urban air pollution is involved in the progress of idiopathic pulmonary fibrosis (IPF). Its potential role on the devastating event of Acute Exacerbation of IPF (AE-IPF) needs to ...be clarified. This study examined the association between long-term personal air pollution exposure and AE- IPF risk taking into consideration inflammatory mediators and telomere length (TL).
Methods
All consecutive IPF-patients referred to our Hospital from October 2013-June 2019 were included. AE-IPF events were recorded and inflammatory mediators and TL measured. Long-term personal air pollution exposures were assigned to each patient retrospectively, for O
3
, NO
2
, PM
2.5
and PM
10
, based on geo-coded residential addresses. Logistic regression models assessed the association of air pollutants’ levels with AE-IPF and inflammatory mediators adjusting for potential confounders.
Results
118 IPF patients (mean age 72 ± 8.3 years) were analyzed. We detected positive significant associations between AE-IPF and a 10 μg/m
3
increase in previous-year mean level of NO
2
(OR = 1.52, 95%CI:1.15–2.0,
p
= 0.003), PM
2.5
(OR = 2.21, 95%CI:1.16–4.20,
p
= 0.016) and PM
10
(OR = 2.18, 95%CI:1.15–4.15,
p
= 0.017) independent of age, gender, smoking, lung function and antifibrotic treatment. Introduction of TL in all models of a subgroup of 36 patients did not change the direction of the observed associations. Finally, O
3
was positively associated with %change of IL-4 (
p
= 0.014) whilst PM
2.5
, PM
10
and NO
2
were inversely associated with %changes of IL-4 (
p
= 0.003,
p
= 0.003,
p
= 0.032) and osteopontin (
p
= 0.013,
p
= 0.013,
p
= 0.085) respectively.
Conclusions
Long-term personal exposure to increased concentrations of air pollutants is an independent risk factor of AE-IPF. Inflammatory mediators implicated in lung repair mechanisms are involved.
The association of ozone exposure with respiratory outcomes has been investigated in epidemiologic studies mainly including asthmatic children. The findings reported had methodological gaps and ...inconsistencies.
We aimed to investigate effects of personal ozone exposure on various respiratory outcomes in school-age children generally representative of the population during their normal activities.
We conducted a panel study in a representative sample of school-age children in the two major cities of Greece, Athens and Thessaloniki. We followed 188, 10- to 11-y-old, elementary school students for 5 wk spread throughout the 2013–2014 academic year, during which ozone was measured using personal samplers. At the end of each study week, spirometry was performed by trained physicians, and the fractional concentration of nitric oxide in exhaled air (
) was measured. Students kept a daily time–activity–symptom diary and measured PEF (peak expiratory flow) using peak flow meters. Mixed models accounting for repeated measurements were applied.
An increase of 10 μg/m
in weekly ozone concentration was associated with a decrease in FVC (forced vital capacity) and FEV
(forced expiratory volume in 1 s) of 0.03 L 95% confidence interval (CI): −0.05, −0.01 and 0.01 L (95% CI: −0.03, 0.003) respectively. The same increase in exposure was associated with a 11.10% (95% CI: 4.23, 18.43) increase in
and 19% (95% CI: −0.53, 42.75) increase in days with any symptom. The effect estimates were robust to PM
adjustment. No inverse association was found between ozone exposure and PEF.
The study provides evidence that airway inflammation and the frequency of respiratory symptoms increase, whereas lung function decreases with increased ozone exposure in schoolchildren. https://doi.org/10.1289/EHP635.
Particulate matter air pollution has been associated with adverse health effects. The fraction of ambient particles that are mainly responsible for the observed health effects is still a matter of ...controversy. Better characterization of the health relevant particle fraction will have major implications for air quality policy since it will determine which sources should be controlled.The RUPIOH study, an EU-funded multicentre study, was designed to examine the distribution of various ambient particle metrics in four European cities (Amsterdam, Athens, Birmingham, Helsinki) and assess their health effects in participants with asthma or COPD, based on a detailed exposure assessment. In this paper the association of central site measurements with respiratory symptoms and restriction of activities is examined.
At each centre a panel of participants with either asthma or COPD recorded respiratory symptoms and restriction of activities in a diary for six months. Exposure assessment included simultaneous measurements of coarse, fine and ultrafine particles at a central site. Data on gaseous pollutants were also collected. The associations of the 24-hour average concentrations of air pollution indices with the health outcomes were assessed in a hierarchical modelling approach. A city specific analysis controlling for potential confounders was followed by a meta-analysis to provide overall effect estimates.
A 10 μg/m3 increase in previous day coarse particles concentrations was positively associated with most symptoms (an increase of 0.6 to 0.7% in average) and limitation in walking (OR= 1.076, 95% CI: 1.026-1.128). Same day, previous day and previous two days ozone concentrations were positively associated with cough (OR= 1.061, 95% CI: 1.013-1.111; OR= 1.049, 95% CI: 1.016-1.083 and OR= 1.059, 95% CI: 1.027-1.091, respectively). No consistent associations were observed between fine particle concentrations, nitrogen dioxide and respiratory health effects. As for particle number concentrations negative association (mostly non-significant at the nominal level) was observed with most symptoms whilst the positive association with limitation of activities did not reach the nominal level of significance.
The observed associations with coarse particles are in agreement with the findings of toxicological studies. Together they suggest it is prudent to regulate also coarse particles in addition to fine particles.
Ambient particulate matter (PM) has an adverse effect on respiratory morbidity. Desert dust outbreaks contribute to increased PM levels but the toxicity of desert dust mixed with anthropogenic ...pollutants needs clarification.
We identified 132 days with desert dust episodes and 177 matched days by day of the week, season, temperature and humidity between 2001 and 2006 in Athens, Greece. We collected data on regulated pollutants and daily emergency outpatient visits and admissions for respiratory causes. We applied Poisson regression models adjusting for confounding effects of seasonality, meteorology, holidays and influenza epidemics. We evaluated the sensitivity of our results to co-pollutant exposures and effect modification by age and sex.
A 10 μg/m
increase in PM
concentration was associated with 1.95% (95% confidence interval (CI): 0.02%, 3.91%) increase in respiratory emergency room visits. No significant interaction with desert dust episodes was observed. Compared with non-dust days, there was a 47% (95% CI: 29%, 68%) increase in visits in dust days not adjusting for PM
. Desert dust days were associated with higher numbers of emergency room visits for asthma, chronic obstructive pulmonary disease and respiratory infections with increases of 38%, 57% and 60%, respectively (p < 0.001 for all comparisons). Analyses of respiratory hospital admissions provided similar results. PM
effects decreased when adjusting for desert dust days and were further confounded by co-pollutants.
Desert dust episode days are associated with higher respiratory emergency room visits and hospital admissions. This effect is insufficiently explained by increased PM
levels.
Background: The coronavirus disease (COVID-19) pandemic has posed an unprecedented challenge to health systems, and has significantly affected the healthcare of lung cancer patients. The aim of our ...study was to assess the impact of COVID-19 on early lung cancer patients’ surgical treatment. Methods: All consecutive patients with early-stage non-small cell lung cancer eligible for surgical treatment stage I/II and resectable stage III, referred to our department during the first wave of COVID-19 between February to May 2020, were included and compared with those on the exact corresponding quarter in 2019, one year before the pandemic. Waiting time to surgical treatment, increase of tumor’s size and increase on lung cancer stage were recorded and compared. All subjects were followed up for 12 months. Multiple linear and logistic regression models were applied to assess the differences in the management of the studied groups adjusting for potential confounders. Results: Sixty-one patients with early-stage lung cancer were included in the study; 28 (median age 67 years, SD: 7.1) during the pandemic and 33 (median age 67.1 years, SD: 7.5) one year earlier. A significantly longer period of waiting for treatment and an increase in tumor size were observed during the pandemic compared to before the pandemic median time 47 days, interquartile rate (IQR): 23−100 vs. median time 18 days, IQR: 11−23, p < 0.001. No significant differences were detected in the increase of the stage of lung cancer between the subgroups. Conclusion: The COVID-19 pandemic had a significant impact on surgical and oncological care, leading to significant delays on treatment and an increase in tumor size in early-stage lung cancer patients.
The number of ultrafine particles in urban air may be more health relevant than the usually measured mass of particles smaller than 2.5 or 10
μm. Epidemiological studies typically assess exposure by ...measurements at a central site. Limited information is available about how well measurements at a central site reflect exposure to ultrafine particles.
The goals of this paper are to assess the relationships between particle number (PN) and mass concentrations measured outdoors at a central site, right outside and inside the study homes. The study was conducted in four European cities: Amsterdam, Athens, Birmingham and Helsinki. Particle mass (PM
10 and PM
2.5), PN, soot and sulfate concentrations were measured at these sites. Measurements of indoors and outdoors near the home were made during 1 week in 152, mostly non-smoking, homes. In each city continuous measurements were also performed at a central site during the entire study period.
The correlation between 24-h average central site outdoor and indoor concentrations was lower for PN (correlation among cities ranged from 0.18 to 0.45) than for PM
2.5 (0.40–0.80), soot (0.64–0.92) and sulfate (0.91–0.99). In Athens, the indoor–central site correlation was similar for PN and PM
2.5. Infiltration factors for PN and PM
2.5 were lower than for sulfate and soot. Night-time hourly average PN concentrations showed higher correlations between indoor and central site, implying that indoor sources explained part of the low correlation found for 24-h average concentrations.
Measurements at a central site may characterize indoor exposure to ambient particles less well for ultrafine particles than for fine particle mass, soot and sulfate.
Idiopathic pulmonary fibrosis acute exacerbation (IPF-AE) constitutes IPF's most devastating event, representing the unexpected superimposition of diffuse alveolar damage of unknown etiology. ...Guidelines recommend high-dose steroids treatment despite unproven benefit. We hypothesized that previous immunosuppression and the administration of high-dose steroids adversely affect IPF-AE outcome.
We studied all consecutive patients hospitalized in our department for IPF deterioration from 2007 to June 2013. Our protocol consisted of immediate cessation of immunosuppression (if any), best supportive care, broad-spectrum antimicrobials and thorough evaluation to detect reversible causes of deterioration. Patients were followed-up for survival; post-discharge none received immunosuppression.
Twenty-four out of 85 admissions (28%) fulfilled IPF-AE criteria. IPF-AE were analyzed both as unique events and as unique patients. As unique events 50% survived; 3 out of 12 (25%) in the group previously treated with immunosuppression whereas nine out of 12 (75%) in the group not receiving immunosuppression (p = 0.041). As unique patients 35.3% survived; 3 out of 6 (50%) in the never treated group whereas three out of 11 (27.3%) in the group receiving immunosuppression (p = 0.685). The history of immunosuppression significantly and adversely influenced survival (p = 0.035). Survival was greater in the never treated group compared to the immunosuppressed patients (p = 0.022). Post-discharge, our IPF-AE survivors had an 83% 1-year survival.
By applying the above mentioned protocol half of our patients survived. The history of immunosuppression before IPF-AE adversely influences survival. Avoiding steroids in IPF patients may favor the natural history of the disease even at the moment of its most devastating event.
Except for a documented increase in osteoprotegerin (OPG) concentrations with older age, data on determinants of soluble Receptor Activator of Nuclear Factor κB (sRANKL) and OPG concentrations in ...women are limited. We evaluated reproductive and lifestyle factors as potential sources of variation in circulating sRANKL and OPG concentrations in pre- and postmenopausal women.
This study includes 2,016 controls
= 1,552 (76%) postmenopausal,
= 757 (38%) using postmenopausal hormone therapy (PMH) from a breast cancer case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Serum sRANKL was measured using an ELISA and serum OPG using an electrochemiluminescent assay. Generalized linear models were used to evaluate associations between these analytes and reproductive and lifestyle factors.
Older age at blood collection was associated with lower sRANKL concentrations in postmenopausal women (
≤ 0.03) and higher OPG concentrations in all women (
≤ 0.01). Longer duration of oral contraceptive use among premenopausal women and postmenopausal PMH users was associated with higher OPG (
≤ 0.04). In postmenopausal non-PMH users, sRANKL concentrations were lower with longer duration of oral contraceptive use and current (vs. never) smoking (
≤ 0.01). sRANKL concentrations were higher among women with higher BMI (
≤ 0.01). The evaluated factors accounted for 12% of the variation in sRANKL concentrations and 21% of the variation in OPG concentrations.
Circulating sRANKL and OPG concentrations are minimally impacted by hormone-related factors in pre- and postmenopausal women.
This study suggests circulating concentrations of sRANKL and OPG are unlikely to be strongly modified by hormone-related reproductive and lifestyle factors.
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