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Air pollution plays an important role in the mortality and morbidity of chronic airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Particulate matter (PM) is a significant fraction of air pollutants, and studies have demonstrated that it can cause airway inflammation and injury. The airway epithelium forms the first barrier of defense against inhaled toxicants, such as PM. Airway epithelial cells clear airways from inhaled irritants and orchestrate the inflammatory response of airways to these irritants by secreting various lipid mediators, growth factors, chemokines, and cytokines. Studies suggest that PM plays an important role in the pathogenesis of chronic airway diseases by impairing mucociliary function, deteriorating epithelial barrier integrity, and inducing the production of inflammatory mediators while modulating the proliferation and death of airway epithelial cells. Furthermore, PM can modulate epithelial plasticity and airway remodeling, which play central roles in asthma and COPD. This review focuses on the effects of PM on airway injury and epithelial plasticity, and the underlying mechanisms involving mucociliary activity, epithelial barrier function, airway inflammation, epithelial-mesenchymal transition, mesenchymal-epithelial transition, and airway remodeling.

Abstract Sound vibration is one of natural stimuli trigging physiological changes in plants. Recent studies showed that sound waves stimulated production of a variety of plant secondary metabolites, including flavonoids, in order to enhance seed germination, flowering, growth or defense. In this review, we examine the potential role of sound stimulation on the biosynthesis of secondary metabolites and the followed cascade of physiological changes in plants, from the perspective of transcriptional regulation and epigenetic regulation for the first time. A systematic summary showed that a wide range of factors may regulate the production of secondary metabolites, including plant species, growth stage, sound types, sound frequency, sound intensity level and exposure time, etc. Biochemical and physiological changes due to sound stimulation were thoroughly summarized as well, for secondary metabolites can also act as a free radical scavenger, or a hormone signaling molecule. We also discussed the limits of previous studies, and the future application of sound waves in biosynthesis of plant secondary metabolites.

The multisystemic effects of COVID-19 may continue for a longer time period following the acute phase, depending on the severity of the disease. However, long-term systemic transcriptomic changes associated with COVID-19 disease and the impact of disease severity are not fully understood. We aimed to investigate the impact of COVID-19 and its severity on transcriptomic alterations in peripheral blood mononuclear cells (PBMCs) following 1 year of the disease. PBMCs were isolated from the peripheral blood of healthy control donors who did not have COVID-19 (C; n = 13), from COVID-19 patients without pneumonia (NP; n = 11), and from COVID-19 patients with severe pneumonia (SP; n = 10) after 1-year of follow-up. Following RNA isolation from PBMCs, high-quality RNAs were sequenced after creating a library. Differentially expressed genes (DEGs) and differentially expressed long non-coding RNAs (DElncRNAs) were identified using Benjamini–Hochberg correction and they were analysed for hierarchical clustering and principal component analysis (PCA). Intergroup comparisons (C vs. NP, C vs. SP, and NP vs. SP) of DEGs and DElncRNAs were performed and hub genes were determined. Functional enrichment analyses of DEGs and DElncRNAs were made using Metascape (v3.5.20240101) and the first version of NCPATH. The RNA sequencing analysis revealed 4843 DEGs and 1056 DElncRNAs in “C vs. NP”, 1651 DEGs and 577 DElncRNAs in “C vs. SP”, and 954 DEGs and 148 DElncRNAs in “NP vs. SP”, with 291 DEGs and 70 DElncRNAs shared across all groups, respectively. We identified 14 hub genes from 291 DEGs, with functional enrichment analysis showing upregulated DEGs mainly linked to inflammation and osteoclast differentiation and downregulated DEGs to viral infections and immune responses. The analysis showed that 291 common and 14 hub genes were associated with pneumonia and that these genes could be regulated by the transcription factors JUN and NFκB1 carrying the NFκB binding site. We also revealed unique immune cell signatures across DEG categories indicating that the upregulated DEGs were associated with neutrophils and monocytes, while downregulated DEGs were associated with CD4 memory effector T cells. The comparative transcriptomic analysis of NP and SP groups with 52 gene signatures suggestive of IPF risk showed a lower risk of IPF in the SP group than the NP patients. Our findings suggest that COVID-19 may cause long term pathologies by modulating the expression of various DEGs, DeLncRNAs, and hub genes at the cellular level.

This paper establishes new results related to geometric function theory by presenting a new subclass of harmonic functions with complex values within the open unit disk, characterized by a second-order differential inequality. The investigation explores the bounds on the coefficients and estimates of the function growth. This paper also demonstrates that this subclass remains stable under the convolution operation applied to its members. In addition, in the last section, images of the unit disk under some functions of this class are given.

Compared to pathogens Pseudomonas aeruginosa and P. putida, P. donghuensis HYS has stronger virulence towards Caenorhabditis elegans. However, the underlying mechanisms haven’t been fully understood. The heme synthesis system is essential for Pseudomonas virulence, and former studies of HemN have focused on the synthesis of heme, while the relationship between HemN and Pseudomonas virulence were barely pursued. In this study, we hypothesized that hemN2 deficiency affected 7-hydroxytropolone (7-HT) biosynthesis and redox levels, thereby reducing bacterial virulence. There are four hemN genes in P. donghuensis HYS, and we reported for the first time that deletion of hemN2 significantly reduced the virulence of HYS towards C. elegans, whereas the reduction in virulence by the other three genes was not significant. Interestingly, hemN2 deletion significantly reduced colonization of P. donghuensis HYS in the gut of C. elegans. Further studies showed that HemN2 was regulated by GacS and participated in the virulence of P. donghuensis HYS towards C. elegans by mediating the synthesis of the virulence factor 7-HT. In addition, HemN2 and GacS regulated the virulence of P. donghuensis HYS by affecting antioxidant capacity and nitrative stress. In short, the findings that HemN2 was regulated by the Gac system and that it was involved in bacterial virulence via regulating 7-HT synthesis and redox levels were reported for the first time. These insights may enlighten further understanding of HemN-based virulence in the genus Pseudomonas.

BackgroundAlthough studies suggest a deficiency in stem cell numbers in chronic airway diseases such as chronic obstructive pulmonary disease (COPD), the role of bronchial epithelial progenitor/stem (P/S) cells is not clear. The objectives of this study were to investigate expression of progenitor/stem (P/S) cell markers, cytokeratin (CK) 5, CK14 and p63 in bronchial epithelial explants and cell cultures obtained from smokers with and without COPD following multiple outgrowths, and to study this effect on bronchial epithelial cell (BEC) proliferation.MethodsBronchial epithelial explants were dissected from lung explants and cultured on coverslips. Confluent cultures were obtained after 3–4 weeks’ (transfer, Tr1), explants were then transferred and cultured for a second (Tr2) and third (Tr3) time, respectively. At each stage, expression of CK5, CK14 and p63 in explants and BEC were determined by immunostaining. In parallel experiments, outgrowing cells from explants were counted after 4wks, and explants subsequently transferred to obtain new cultures for a further 3 times.ResultsAs the transfer number advanced, CK5, CK14 and p63 expression was decreased in both explants and BEC from both smokers without COPD and patients with COPD, with a more pronounced decrease in BEC numbers in the COPD group. Total cell numbers cultured from explants were decreased with advancing outgrowth number in both groups. Smoking status and lung function parameters were correlated with reduced P/S marker expression and cell numbers.ConclusionOur findings suggest that the number of P/S cells in airway epithelium may play a role in the pathogenesis of COPD, as well as a role in the proliferation of airway epithelial cells, in vitro.

ObjectiveIt is known that the inhalation of air pollutants adversely affects human health. These air pollutants originated from natural sources such as desert storms or human activities including traffic, power generating, domestic heating, etc. This study aimed to investigate the impacts of desert dust storms, particulate matter ≤10 μm (PM10) and daily maximum temperature (MT) on mortality and emergency department (ED) visits due to stroke in the city of Gaziantep, Southeast Turkey.MethodThe data on mortality and ED visits due to stroke were retrospectively recruited from January 1, 2009, to March 31, 2014, in Gaziantep City Centre.ResultsPM10 levels did not affect ED visits or mortality due to stroke; however, MT increased both ED visits [adjusted odds ratio (OR) = 1.002, 95% confidence interval (CI) = 1.001–1.003] and mortality (OR = 1.006, 95% CI = 0.997–1.014) due to stroke in women. The presence of desert storms increased ED visits due to stroke in the total population (OR = 1.219, 95% CI = 1.199–1.240), and all subgroups. It was observed that desert dust storms did not have an increasing effect on mortality.ConclusionOur findings suggest that MT and desert dust storms can induce morbidity and mortality due to stroke.

Abstract Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been growing swiftly worldwide. Patients with background chronic pulmonary inflammations such as asthma or chronic obstructive pulmonary diseases (COPD) are likely to be infected with this virus. Of note, there is an argument that COVID-19 can remain with serious complications like fibrosis or other pathological changes in the pulmonary tissue of patients with chronic diseases. Along with conventional medications, regenerative medicine, and cell-based therapy could be alternative approaches to compensate for organ loss or restore injured sites using different stem cell types. Owing to unique differentiation capacity and paracrine activity, these cells can accelerate the healing procedure. In this review article, we have tried to scrutinize different reports related to the harmful effects of SARS-CoV-2 on patients with asthma and COPD, as well as the possible therapeutic effects of stem cells in the alleviation of post-COVID-19 complications. Video abstract

Abstract Chronic obstructive pulmonary disease (COPD) is known as the third leading cause of human death globally. Enhanced chronic inflammation and pathological remodeling are the main consequences of COPD, leading to decreased life span. Histological and molecular investigations revealed that prominent immune cell infiltration and release of several cytokines contribute to progressive chronic remodeling. Recent investigations have revealed that exosomes belonging to extracellular vesicles are involved in the pathogenesis of COPD. It has been elucidated that exosomes secreted from immune cells are eligible to carry numerous pro-inflammatory factors exacerbating the pathological conditions. Here, in this review article, we have summarized various and reliable information about the negative role of immune cell-derived exosomes in the remodeling of pulmonary tissue and airways destruction in COPD patients.

Chronic obstructive pulmonary disease is a progressive and incurable chronic condition that involves accumulation of inflammatory macrophages in the lung tissue. Authors here show in mouse models of lung disease that PRMT7, a protein arginine methyltransferase, is an important regulator of recruitment and the pro-inflammatory phenotype of macrophages.

This paper introduces two novel subclasses of the function class Σ for bi-univalent functions, leveraging generalized telephone numbers and Binomial series through convolution. The exploration is conducted within the domain of the open unit disk. We delve into the analysis of initial Taylor-Maclaurin coefficients |a2| and |a3|, deriving insights and findings for functions belonging to these new subclasses. Additionally, Fekete-Szegö inequalities are established for these functions. Furthermore, the study unveils a range of new subclasses of Σ, some of which are special cases, yet have not been previously explored in conjunction with telephone numbers. These subclasses emerge as a result of hybrid-type convolution operators. Concluding from our results, we present several corollaries, which stand as fresh contributions in the domain of involution numbers involving hybrid-type convolution operators.

The Theory of Complex Functions has been studied by many scientists and its application area has become a very wide subject. Harmonic functions play a crucial role in various fields of mathematics, physics, engineering, and other scientific disciplines. Of course, the main reason for maintaining this popularity is that it has an interdisciplinary field of application. This makes this subject important not only for those who work in pure mathematics, but also in fields with a deep-rooted history, such as engineering, physics, and software development. In this study, we will examine a subclass of Harmonic functions in the Theory of Geometric Functions. We will give some definitions necessary for this. Then, we will define a new subclass of complex-valued harmonic functions, and their coefficient relations, growth estimates, radius of univalency, radius of starlikeness and radius of convexity of this class are investigated. In addition, it is shown that this class is closed under convolution of its members.

Objective: To determine post-discharge mortality and associated factors of the first-wave multicenter Turkish Thoracic Society (TTD)-TURCOVID study. Methods: In this retrospective cohort study, we analyzed the data of 18 of 26 centers included in the first TTD-TURCOVID study, and 1 112 cases diagnosed with COVID-19 between 11 March and 31 July 2020 participated in the study. All causes of death after COVID-19 discharge were recorded. Results: The mean age of the patients was (51.07±16.93) years, with 57.6% male patients. In the cohort group, 89.1% of COVID-19 treatment locations were hospital wards, 3.6% were intensive care units (ICUs), and 7.2% were community outpatients. In the longterm follow-up, the in-hospital mortality rate was 3.6% (95% CI 2.64.8), the post-discharge mortality rate was 2.8% (95% CI 1.9-3.9), and the total mortality was 6.3% (95% CI 5.0-7.8). After discharge, 63.3% of mortality overall occurred during the first six months. Mortality rates in post-discharge follow-ups were 12.7% (95% CI 8.0-30.6) in cancer patients, 10.8% (95% CI 6.3-22.9) in chronic obstructive pulmonary disease patients, 11.1% (95% CI 4.4-22.7) in heart failure patients, 7.8 (95% CI 3.8-14.3) in atherosclerotic heart disease patients, and 2.3% (95% CI 0.8-5.6) in diabetes mellitus patients. In smokers/ex-smokers, the all-mortality rates were higher than in non-smokers. Conclusions: This multicenter study showed that patients over 65 years of age, males, former/active smoker, ICU stay, lung, heart disease, and malignancy should be followed up for at least the first six months after discharge due to COVID-19.

Objective: To evaluate long-term effects of COVID-19, and to determine the risk factors in long-COVID in a cohort of the Turkish Thoracic Society (TTS)-TURCOVID multicenter registry. Methods: Thirteen centers participated with 831 patients; 504 patients were enrolled after exclusions. The study was designed in three-steps: (1) Phone questionnaire; (2) retrospective evaluation of the medical records; (3) face-to-face visit. Results: In the first step, 93.5% of the patients were hospitalized; 61.7% had a history of pneumonia at the time of diagnosis. A total of 27.1% reported clinical symptoms at the end of the first year. Dyspnea (17.00%), fatigue (6.30%), and weakness (5.00%) were the most prevalent long-term symptoms. The incidence of long-term symptoms was increased by 2.91 fold (95% CI 1.04-8.13, P=0.041) in the presence of chronic obstructive pulmonary disease and by 1.84 fold (95% CI 1.10-3.10, P=0.021) in the presence of pneumonia at initial diagnosis, 3.92 fold (95% Cl 2.29-6.72, P=0.001) of dyspnea and 1.69 fold (95% Cl 1.02-2.80, P=0.040) fatigue persists in the early-post-treatment period and 2.88 fold (95% Cl 1.52- 5.46, P=0.001) in the presence of emergency service admission in the post COVID period. In step 2, retrospective analysis of 231 patients revealed that 1.4% of the chest X-rays had not significantly improved at the end of the first year, while computed tomography (CT) scan detected fibrosis in 3.4%. In step 3, 138 (27.4%) patients admitted to face-to-face visit at the end of first year; at least one symptom persisted in 49.27% patients. The most common symptoms were dyspnea (27.60%), psychiatric symptoms (18.10%), and fatigue (17.40%). Thorax CT revealed fibrosis in 2.4% patients. Conclusions: COVID-19 symptoms can last for extended lengths of time, and severity of the disease as well as the presence of comorbidities might contribute to increased risk. Long-term clinical issues should be regularly evaluated after COVID-19.

Abstract Malignant pleural mesothelioma (MPM) arises from mesothelial cells lining the pleural cavity of asbestos‐exposed individuals and rapidly leads to death. MPM harbors loss‐of‐function mutations in BAP1, NF2, CDKN2A, and TP53, but isolated deletion of these genes alone in mice does not cause MPM and mouse models of the disease are sparse. Here, we show that a proportion of human MPM harbor point mutations, copy number alterations, and overexpression of KRAS with or without TP53 changes. These are likely pathogenic, since ectopic expression of mutant KRASG12D in the pleural mesothelium of conditional mice causes epithelioid MPM and cooperates with TP53 deletion to drive a more aggressive disease form with biphasic features and pleural effusions. Murine MPM cell lines derived from these tumors carry the initiating KRASG12D lesions, secondary Bap1 alterations, and human MPM‐like gene expression profiles. Moreover, they are transplantable and actionable by KRAS inhibition. Our results indicate that KRAS alterations alone or in accomplice with TP53 alterations likely play an important and underestimated role in a proportion of patients with MPM, which warrants further exploration.

Take Home Message: Capsaicin modified inflammatory response and caused toxicity in bronchial epithelial cultures from patients with COPD. More importantly, capsaicin decreased ciliary beat frequency and induced epithelial permeability and these effects were partially prevented by formoterol and roflumilast.Tear gas is widely used to halt mass demonstrations. Studies have reported its adverse effects on multiple organ systems; however, its effect on individuals with chronic respiratory diseases and the underlying mechanisms of these effects are unclear. For the first time in the literature, we investigated the effects of capsaicin, the active ingredient of tear gas, on bronchial epithelial cell (BEC) cultures obtained from well-characterized groups of nonsmokers, smokers, and patients with chronic obstructive pulmonary disease (COPD). BEC cultures were incubated with 50-500 μM capsaicin in the absence and presence of formoterol (1μM) and roflumilast (0.1 μM) for 24 h. Ciliary beat frequency (CBF) and transepithelial electrical resistance (TEER) were assessed at T1/4, T1/2, T1, T2, T4, T6, and T24 h, whereas the release of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-8, and lactate dehydrogenase (LDH) was measured at T24 h. Capsaicin (250 µM) significantly decreased CBF of all BEC cultures from T1/4 h to T24 h (p

Background and objectivesAlthough several repurposed antiviral drugs have been used for the treatment of COVID-19, only a few such as remdesivir and molnupiravir have shown promising effects. The objectives of our study were to investigate the association of repurposed antiviral drugs with COVID-19 morbidity.MethodsPatients admitted to 26 different hospitals located in 16 different provinces between March 11–July 18, 2020, were enrolled. Case definition was based on WHO criteria. Patients were managed according to the guidelines by Scientific Board of Ministry of Health of Turkey. Primary outcomes were length of hospitalization, intensive care unit (ICU) requirement, and intubation.ResultsWe retrospectively evaluated 1,472 COVID-19 adult patients; 57.1% were men (mean age = 51.9 ± 17.7years). A total of 210 (14.3%) had severe pneumonia, 115 (7.8%) were admitted to ICUs, and 69 (4.7%) were intubated during hospitalization. The median (interquartile range) of duration of hospitalization, including ICU admission, was 7 (5–12) days. Favipiravir (n = 328), lopinavir/ritonavir (n = 55), and oseltamivir (n = 761) were administered as antiviral agents, and hydroxychloroquine (HCQ, n = 1,382) and azithromycin (n = 738) were used for their immunomodulatory activity. Lopinavir/ritonavir (β [95% CI]: 4.71 [2.31–7.11]; p = 0.001), favipiravir (β [95% CI]: 3.55 [2.56–4.55]; p = 0.001) and HCQ (β [95% CI]: 0.84 [0.02–1.67]; p = 0.046) were associated with increased risk of lengthy hospital stays. Furthermore, favipiravir was associated with increased risks of ICU admission (OR [95% CI]: 3.02 [1.70–5.35]; p = 0.001) and invasive mechanical ventilation requirement (OR [95% CI]: 2.94 [1.28–6.75]; p = 0.011).ConclusionOur findings demonstrated that antiviral drugs including lopinavir, ritonavir, and favipiravir were associated with negative clinical outcomes such as increased risks for lengthy hospital stay, ICU admission, and invasive mechanical ventilation requirement. Therefore, repurposing such agents without proven clinical evidence might not be the best approach for COVID-19 treatment.

In this paper, various features of a new class of normalized multivalent harmonic functions in the open unit disk are analyzed, including bounds on coefficients, growth estimations, starlikeness and convexity radii. It is further demonstrated that this class is closed when its members are convoluted. It can also be seen that various previously introduced and investigated classes of multivalent harmonic functions appear as special cases for this class.

We preface and examine classes of (p, q)-convex harmonic locally univalent functions associated with subordination. We acquired a coefficient characterization of (p, q)-convex harmonic univalent functions. We give necessary and sufficient convolution terms for the functions we will introduce.

In late December 2019, a vtiral pneumonia with an unknown agent was reported in Wuhan, China. A novel coronavirus was identified as the causative agent. Because of the human-to-human transmission and rapid spread; coronavirus disease 2019 (COVID-19) has rapidly increased to an epidemic scale and poses a severe threat to human health; it has been declared a public health emergency of international concern (PHEIC) by the World Health Organization (WHO). This review aims to summarize the recent research progress of COVID-19 molecular features and immunopathogenesis to provide a reference for further research in prevention and treatment of SARS coronavirus2 (SARS-CoV-2) infection based on the knowledge from researches on SARS-CoV and Middle East respiratory syndrome-related coronavirus (MERS-CoV).

In this article, we introduce and investigate the q-analogue of a new subclass of harmonic univalent functions defined by subordination. We first obtain a coefficient characterization of these functions. We give compactness and extreme points, distortion bounds, necessary and sufficient convolution conditions for this subclass of harmonic univalent functions with negative coefficients. The symmetry properties and other properties of the q-analogue subclass of functions presented in this paper shed light on future studies.

Abstract The development of chronic obstructive pulmonary disease (COPD) pathogenesis remains unclear, but emerging evidence supports a crucial role for inducible bronchus‐associated lymphoid tissue (iBALT) in disease progression. Mechanisms underlying iBALT generation, particularly during chronic CS exposure, remain to be defined. Oxysterol metabolism of cholesterol is crucial to immune cell localization in secondary lymphoid tissue. Here, we demonstrate that oxysterols also critically regulate iBALT generation and the immune pathogenesis of COPD. In both COPD patients and cigarette smoke (CS)‐exposed mice, we identified significantly upregulated CH25H and CYP7B1 expression in airway epithelial cells, regulating CS‐induced B‐cell migration and iBALT formation. Mice deficient in CH25H or the oxysterol receptor EBI2 exhibited decreased iBALT and subsequent CS‐induced emphysema. Further, inhibition of the oxysterol pathway using clotrimazole resolved iBALT formation and attenuated CS‐induced emphysema in vivo therapeutically. Collectively, our studies are the first to mechanistically interrogate oxysterol‐dependent iBALT formation in the pathogenesis of COPD, and identify a novel therapeutic target for the treatment of COPD and potentially other diseases driven by the generation of tertiary lymphoid organs.

Chronic obstructive pulmonary disease and asthma affect millions of people worldwide. Conventional treatments are not sufficient at preventing the progression of these diseases. The treatments are unspecific, and when administered systematically, and in high doses, they have adverse health effects. Further, the current diagnostic methods are poor and they are not capable of identifying the accurate state of the disease. Nanoparticle-based theranostics (NBTs) are well-established systems that simultaneously provide treatment and diagnostics. Various nanocarriers can be used in NBT and are designed according to the need. In this review, liposome-based theranostic systems are evaluated and possible modifications that could provide better drug delivery and accumulation and diagnosis are exemplified. These systems can be applied to conventional therapeutics to avoid side effects and perhaps overcome the challenges that interfere with their cellular accumulation.

Objective. This study was designed to investigate the effects of Desert Dust Storms and Climatological Factors on Mortality and Morbidity of Cardiovascular Diseases admitted to emergency department in Gaziantep. Method. Hospital records, obtained between September 01, 2009 and January 31, 2014, from four state hospitals in Gaziantep, Turkey, were compared to meteorological and climatological data. Statistical analysis was performed by Statistical Package for the Social Science (SPSS) for windows version 24.0. Results. 168,467 patients were included in this study. 83% of the patients had chest pain and 17% of patients had cardiac failure (CF). An increase in inpatient hospitalization due to CF was observed and corresponded to the duration of dust storms measured by number of days. However, there was no significant increase in emergency department (ED) presentations. There was no significant association of cardiac related mortality and coinciding presence of a dust storm or higher recorded temperature. The association of increases in temperature levels and the presence of dust storms with “acute coronary syndrome- (ACS-) related emergency service presentations, inpatient hospitalization, and mortality” were statistically significant. The relationship between the increase in PM10 levels due to causes unrelated to dust storms and the outpatient application, admission, and mortality due to heart failure was not significant. The increase in particle matter 10 (PM) levels due to causes outside the dust storm caused a significant increase in outpatient application, hospitalization, and mortality originated from ACS. Conclusion. Increased number of dust storms resulted in a higher prevalence of mortality due to ACS while mortality due to heart failure remained unchanged. Admission, hospitalization, and mortality due to chest pain both dependent and independent of ACS were increased by the presence of dust storms, PM10 elevation, and maximum temperature.

The prevalence of allergic airway diseases such as asthma and rhinitis has increased dramatically to epidemic proportions worldwide. Besides air pollution from industry derived emissions and motor vehicles, the rising trend can only be explained by gross changes in the environments where we live. The world economy has been transformed over the last 25 years with developing countries being at the core of these changes. Around the planet, in both developed and developing countries, environments are undergoing profound changes. Many of these changes are considered to have negative effects on respiratory health and to enhance the frequency and severity of respiratory diseases such as asthma in the general population.Increased concentrations of greenhouse gases, and especially carbon dioxide (CO2), in the atmosphere have already warmed the planet substantially, causing more severe and prolonged heat waves, variability in temperature, increased air pollution, forest fires, droughts, and floods – all of which can put the respiratory health of the public at risk. These changes in climate and air quality have a measurable impact not only on the morbidity but also the mortality of patients with asthma and other respiratory diseases. The massive increase in emissions of air pollutants due to economic and industrial growth in the last century has made air quality an environmental problem of the first order in a large number of regions of the world. A body of evidence suggests that major changes to our world are occurring and involve the atmosphere and its associated climate. These changes, including global warming induced by human activity, have an impact on the biosphere, biodiversity, and the human environment. Mitigating this huge health impact and reversing the effects of these changes are major challenges.This statement of the World Allergy Organization (WAO) raises the importance of this health hazard and highlights the facts on climate-related health impacts, including: deaths and acute morbidity due to heat waves and extreme meteorological events; increased frequency of acute cardio-respiratory events due to higher concentrations of ground level ozone; changes in the frequency of respiratory diseases due to trans-boundary particle pollution; altered spatial and temporal distribution of allergens (pollens, molds, and mites); and some infectious disease vectors. According to this report, these impacts will not only affect those with current asthma but also increase the incidence and prevalence of allergic respiratory conditions and of asthma. The effects of climate change on respiratory allergy are still not well defined, and more studies addressing this topic are needed. Global warming is expected to affect the start, duration, and intensity of the pollen season on the one hand, and the rate of asthma exacerbations due to air pollution, respiratory infections, and/or cold air inhalation, and other conditions on the other hand.

Epidemiological studies have demonstrated that there is an association between increases in air pollution and cardiopulmonary mortality and morbidity. Multi-center studies in North America and Western European countries reported that an increase in the levels of particulate matter (PM), ozone, nitrogen oxides (NOx) and sulphur dioxide (SO2) leads to increases in prevalence, emergency room visits and hospitalization due to chronic respiratory diseases such as asthma and chronic obstructive disease (COPD). Furthermore, it has been shown that increased levels of air pollutants are associated with increased prevalence of respiratory infections, including pneumonia. Although studies of indoor air pollution clearly showed a significant association with tuberculosis (TB), studies investigating the role of outdoor air pollution are lacking. However, it has recently been reported that increased ambient levels of air pollutants such as PM≤2.5 μm and SO2 were associated with increased risk of TB. In vivo human studies demonstrated that exposure to ozone, NO2 and diesel exhaust (DE) leads to irritation in the mouth and nose, dyspnoea, wheezing, chest tightness, decreases in lung function tests, and increased airway hyper-responsiveness. There were also increased levels of neutrophils, lymphocytes and inflammatory mediators in bronchial lavage and bronchial biopsies of subjects exposed to ozone and DE. Furthermore, SO2 and NO2 increased airway response of allergic asthmatic subjects to allergens, such as house dust mite allergen. In vitro studies reported that DE particles (DEP) induce inflammatory mediator expression and synthesis of IgE specific to allergens in human B cells. Studies of human macrophages demonstrated that fine carbon black (CB) induced inflammatory cytokines and impaired phagocytosis of pneumococci and mycobacteria TB with a reduction in the oxidative burst capacity of these cells. This study has demonstrated that DEP, which constitute an important fraction of PM pollution, can decrease ciliary beat frequency (CBF), and induce the release of inflammatory mediators such as interleukin (IL)-8, granulocyte macrophage-colony stimulating factor (GM-CSF), normal T-cell expressed and secreted (RANTES) and soluble intercellular adhesion molecule (sICAM)-1 from primary bronchial epithelial cells (BECs). More recently, this study found that DEP can decrease airway epithelial cell viability and modify the cell cycle progression and apoptosis by inducing oxidative stress-related pathways, such as activator protein (AP)-1 and nuclear factor (NF)-κB, and an increased expression of apoptosis and cell cycle regulating proteins such as p21, p27, p53, cyclin E, c-myc, and cyclin-dependant kinase 2 (CDK2). Interestingly, serum, as can be seen in the inflamed airways of patients with chronic airway diseases such as asthma and COPD because of extravasation, enhanced the detrimental effects of DEP. Furthermore, these studies showed that gaseous air pollutants such as ozone and NO2 induce permeability of BEC cultures with an increase in the release of inflammatory mediators. More importantly, this study demonstrated that BECs from patients with chronic airway diseases such as asthma and COPD are more susceptible to deleterious effects of air pollutants. In conclusion, air pollutants can induce respiratory mortality and morbidity by leading to airway and lung inflammation and impairing the airway defence system against noxious agents and microorganisms such as mycobacteria TB.