Preexisting Airway Disease Research Articles

Long-term impact of COVID-19 hospitalisation among individuals with pre-existing airway diseases in the UK: a multicentre, longitudinal cohort study - PHOSP-COVID.

The long-term outcomes of COVID-19 hospitalisation in individuals with pre-existing airway diseases are unknown. Adult participants hospitalised for confirmed or clinically suspected COVID-19 and discharged between 5 March 2020 and 31 March 2021 were recruited to the Post-hospitalisation COVID-19 (PHOSP-COVID) study. Participants attended research visits at 5 months and 1 year post discharge. Clinical characteristics, perceived recovery, burden of symptoms and health-related quality of life (HRQoL) of individuals with pre-existing airway disease (i.e., asthma, COPD or bronchiectasis) were compared to the non-airways group. A total of 615 out of 2697 (22.8%) participants had a history of pre-existing airway diseases (72.0% diagnosed with asthma, 22.9% COPD and 5.1% bronchiectasis). At 1 year, the airways group participants were less likely to feel fully recovered (20.4% versus 33.2%, p<0.001), had higher burden of anxiety (29.1% versus 22.0%, p=0.002), depression (31.2% versus 24.7%, p=0.006), higher percentage of impaired mobility using short physical performance battery ≤10 (57.4% versus 45.2%, p<0.001) and 27% had a new disability (assessed by the Washington Group Short Set on Functioning) versus 16.6%, p=0.014. HRQoL assessed using EQ-5D-5L Utility Index was lower in the airways group (mean±SD 0.64±0.27 versus 0.73±0.25, p<0.001). Burden of breathlessness, fatigue and cough measured using a study-specific tool was higher in the airways group. Individuals with pre-existing airway diseases hospitalised due to COVID-19 were less likely to feel fully recovered, had lower physiological performance measurements, more burden of symptoms and reduced HRQoL up to 1 year post-hospital discharge.

New Automated Method for Lung Functional Volumes Delineation with Lung Perfusion PET/CT Imaging.

Gallium-68 lung perfusion PET/CT is an emerging imaging modality for the assessment of regional lung function, especially to optimise radiotherapy (RT) planning. A key step of lung functional avoidance RT is the delineation of lung functional volumes (LFVs) to be integrated into radiation plans. However, there is currently no consistent and reproducible delineation method for LFVs. The aim of this study was to develop and evaluate an automated delineation threshold method based on total lung function for LFVs delineation with Gallium-68 MAA lung PET/CT imaging. Patients prospectively enrolled in the PEGASUS trial-a pilot study assessing the feasibility of lung functional avoidance using perfusion PET/CT imaging for lung stereotactic body radiotherapy (SBRT) of primary or secondary lesion-were analysed. Patients underwent lung perfusion MAA-68Ga PET/CT imaging and pulmonary function tests (PFTs) as part of pre-treatment evaluation. LFVs were delineated using two methods: the commonly used relative to the maximal pixel value threshold method (pmax threshold method, X%pmax volumes) and a new approach based on a relative to whole lung function threshold method (WLF threshold method, FVX% volumes) using a dedicated iterative algorithm. For both methods, LFVs were expressed in terms of % of the anatomical lung volume (AV) and of % of the total lung activity. Functional volumes were compared for patients with normal PFTs and pre-existing airway disease. 60 patients were analysed. Among the 48 patients who had PFTs, 31 (65%) had pre-existing lung disease. The pmax and WLF threshold methods clearly provided different functional volumes with a wide range of relative lung function for a given pmax volume, and conversely, a wide range of corresponding pmax values for a given WLF volume. The WLF threshold method provided more reliable and consistent volumes with much lower dispersion of LFVs as compared to the pmax method, especially in patients with normal PFTs. We developed a relative to whole lung function threshold segmentation method to delineate lung functional volumes on perfusion PET/CT imaging. The automated algorithm allows for reproducible contouring. This new approach, relatively unaffected by the presence of hot spots, provides reliable and consistent functional volumes, and is clinically meaningful for clinicians.

Changing patterns of pulmonary abnormalities in rheumatoid arthritis.

As a first step in identifying the developmental pathways of pulmonary abnormalities in rheumatoid arthritis (RA), we sought to determine the existing and changing patterns of pulmonary abnormalities. We conducted a retrospective cohort study of consecutive patients with RA who underwent high-resolution computed tomography before and during biologic therapy. The presence of 20 pulmonary abnormalities and the changes in those abnormalities were recorded. Patterns of pre-existing and changing abnormalities were examined via cluster analysis, and their relationship was also assessed using the Kaplan-Meier method and log-rank test. A total of 208 subjects were included. Pulmonary abnormalities were observed in 70% of patients: 39% had interstitial lung disease, and 55% had airway disease (AD). Several different pulmonary abnormalities were commonly found to co-exist in several patterns in the same patient. In most patients with pulmonary abnormalities, AD was present alone or in combination with other abnormalities. During the observation period (mean 3.2 years), 172 pulmonary abnormalities had changed in 91 patients: 115 pulmonary abnormalities newly emerged, whereas 42 worsened and 25 demonstrated improvement. Pulmonary abnormalities changed in several patterns. Correlations were observed between pre-existing and new/worsening abnormalities at individual and regional levels, such as new ground-glass opacity (GGO) and pre-existing AD, small nodular patterns, and honeycombing. AD was a possible initial abnormality. Pulmonary abnormalities occurred and changed in several patterns, which suggests the existence of developmental pathways of pulmonary abnormalities. AD may play an important role in the development of these abnormalities, including GGO.

Reply: Does a Capsulectomy Really Improve Pulmonary Function in Women with Breast Implant Illness?

Sir: We thank Dr. E. Swanson for his comments regarding our recent publication.1 The purpose of studying respiratory function in this group of breast implant illness patients was due to the clinical observation that they could breathe better and more deeply with less effort after implant removal and capsulectomy. We developed a quantitative symptomatic data tool to study the outcomes of explantation with capsulectomy.1 These studies were our attempt to provide evidence-based information about this specific group of patients.2,3 The improvement in pulmonary function experienced by these patients may have many complex etiologies. One of these may be the weight on the chest. The effect of breast hypertrophy on pulmonary function has been studied in multiple studies.4–8 The relief of weight can have a beneficial effect on pulmonary function. Another etiology for improvement may be the relief of scarring on chest wall in improving chest wall mechanics in breathing. It is important to note that for these patients, the decision to explant is challenging. Not only do they feel that they have to undo an augmentation surgery that they once desired, but they also have to face potential deformity resulting from years of implantation. Their decision is purely based upon the possibility that their health could be improved. The diagnosis of breast implant illness is also not an easy one. These 11 symptoms can mimic Lyme disease, hypothyroidism, menopause, autoimmune disease, or multiple sclerosis. The diagnosis of breast implant illness is based upon a diagnosis of exclusion and improvement of symptoms following implant removal and capsulectomy. This study is not a randomized controlled study comparing implant removal with capsulectomy versus implant removal without capsulectomy. This type of study is ideal, but clinically challenging to execute practically. Total capsulectomy can be associated with increased complications. We did not report any complications from the 750-patient or 72-patient cohort related to pneumothorax complication. There is a clearly defined plane between the capsule and the external intercostal muscle. When you separate the capsule from the external intercostal muscle and you preserve this muscle, pneumothorax can be avoided. Bleeding complications have occurred, but in less than 1% of the group. The selection criteria for the respiratory study3 are well-defined in our methods section. Only those patients who were able to return for a repeat spirometry after explantation were included. We have excluded patients with pre-existing airway and parenchymal disease such as asthma and COPD. That leaves 69 patients for statistical analysis. The exclusion rate is 4%. We did not use a t-test for independent samples of means because the variables that we were testing, before and after capsulectomy, came from the same patient. Therefore, the paired t-test was more appropriately utilized. The online t-test or independent samples t-test is a less powerful and ideal t-test for this study because the same individuals are being measured before and after explant. The paired t-test was used to account for within patient variations. TheP values in the paired t-test for FVC (P = 0.008), FEV1 (P = 0.009), and PEFR (P = 0.001) have all met the rigorous level of less than 0.01. In the multivariate and univariate analysis, both FEV1 P values of 0.009 for univariate analysis and 0.018 P value for multivariate analysis for the textured versus smooth implants are considered significant. We look forward to future study of this under characterized patient population to better answer the thoughtful critiques and questions described by Dr. Swanson and many other accomplished surgeons caring for patients with symptomatic breast implants. DISCLOSURE The authors have no financial interest to declare in relation to the content of this article.

The Survival of Patients With Alveolar Hemorrhage Secondary to Antineutrophil Cytoplasmic Antibody–associated Vasculitis

Diffuse alveolar hemorrhage (DAH) is a clinical syndrome that can be caused by a variety of nonimmune-mediated and immune-mediated etiologies, including antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). DAH is one of the most severe and life-threatening manifestations of AAV, occurring in up to 25% of patients with AAV1. Some studies have suggested that DAH may be more common in microscopic polyangiitis (MPA) than in granulomatosis with polyangiitis (GPA), but reported frequencies may be affected by factors including variable epidemiology of MPA versus GPA in different regions of the world, applied disease definitions, and local referral patterns to tertiary care centers2,3,4,5. Preexisting airway disease has been reported as an independent risk factor for the development of DAH in AAV3. Irrespective of the frequency and severity of DAH in AAV, there is only a limited number of studies addressing the prognosis of DAH in patients with AAV (Table 1). The combination of glucocorticoids (GC) with cyclophosphamide (CYC) or rituximab (RTX), variably combined with plasma exchange (PLEX), is usually effective to induce remission of the disease in the majority of patients, and the main causes of death are infections or cardiovascular complications rather than vasculitis activity2,6,7,8,9,10. View this table: Table 1. The published cohorts of DAH occurring in patients with AAV (only studies with ≥ 20 patients are reported). In this issue of The Journal , Tang and colleagues11 report on their analysis of clinical features at presentation and the main prognostic factors of DAH in a single-center cohort of 92 patients with MPA. This is the largest cohort of DAH in patients with MPA published so far. Interestingly, in this cohort, the mortality was the highest reported for DAH in patients with … Address correspondence to Dr. A. Berti, Rheumatology Department, Santa Chiara Hospital, Largo Medaglie D’Oro 9, 38121, Trento, Trentino, Italy. Email: alvise.berti{at}apss.tn.it.

Measurement of subglottic diameter and distance to pre-epiglottic space among Chinese adults.

Proper endotracheal tube (ETT) size selection and identification of potentially difficult airways are important to reduce laryngeal injury during intubation. However, controversies exist concerning transverse subglottic diameter-the narrowest part of the airway-and the distance to pre-epiglottic space. Because few studies have reported the distance from skin to the midpoint of the epiglottis (DSE) among normal individuals, whether the DSE varies between individuals and by ethnicity remains uncertain. The present study aims to investigate the sonographic subglottic diameter and DSE among healthy Chinese adults. Healthy volunteers were recruited at National Taiwan University Hospital between October and November 2019. Exclusion criteria included pre-existing airway or respiratory diseases, neck tumors, and a history of neck operation. Age, sex, height, weight, body mass index (BMI), sonographic DSE, and transverse subglottic diameter were recorded. A total of 124 participants were enrolled. The average age was 32.5 ± 10.4 years and 63 participants (51%) were males. The subglottic diameter was positively associated with sex (males, 14.40 mm; females, 11.10 mm, p < 0.001) and BMI (underweight, 12.13 mm; normal weight, 12.47 mm; overweight, 13.80 mm; obese, 13.67 mm, p = 0.007). Moreover, the DSE was shorter in males (male, 16.18 mm; females, 14.54 mm, p < 0.001) and participants with increased BMI (underweight, 13.70 mm; normal weight, 15.06 mm; overweight, 16.58 mm; obese, 18.18 mm, p < 0.001). As compared with other ethnicity, a smaller size of subglottic diameter and a shorter DSE were noted among Chinese participants, and we suggest that a relatively smaller size of endotracheal tube selection should be considered in tracheal intubations.

Outdoor Air Pollution and New-Onset Airway Disease. An Official American Thoracic Society Workshop Report.

Although it is well accepted that air pollution exposure exacerbates preexisting airway disease, it has not been firmly established that long-term pollution exposure increases the risk of new-onset asthma or chronic obstruction pulmonary disease (COPD). This Workshop brought together experts on mechanistic, epidemiological, and clinical aspects of airway disease to review current knowledge regarding whether air pollution is a causal factor in the development of asthma and/or COPD. Speakers presented recent evidence in their respective areas of expertise related to air pollution and new airway disease incidence, followed by interactive discussions. A writing committee summarized their collective findings. The Epidemiology Group found that long-term exposure to air pollution, especially metrics of traffic-related air pollution such as nitrogen dioxide and black carbon, is associated with onset of childhood asthma. However, the evidence for a causal role in adult-onset asthma or COPD remains insufficient. The Mechanistic Group concluded that air pollution exposure can cause airway remodeling, which can lead to asthma or COPD, as well as asthma-like phenotypes that worsen with long-term exposure to air pollution, especially fine particulate matter and ozone. The Clinical Group concluded that air pollution is a plausible contributor to the onset of both asthma and COPD. Available evidence indicates that long-term exposure to air pollution is a cause of childhood asthma, but the evidence for a similar determination for adult asthma or COPD remains insufficient. Further research is needed to elucidate the exact biological mechanism underlying incident childhood asthma, and the specific air pollutant that causes it.

Association between preexisting lung involvements and the risk of diffuse alveolar hemorrhage in patients with microscopic polyangiitis: A multi-center retrospective cohort study

Objectives: To identify the factors associated with the risk of diffuse alveolar hemorrhage (DAH) in patients with microscopic polyangiitis (MPA), focusing on other preexisting lung involvements such as interstitial lung disease (ILD) and airway disease.Methods: In this retrospective cohort study, we analyzed consecutive patients with myeloperoxidase-antineutrophil cytoplasmic antibody-positive MPA who had undergone chest computed tomography (CT) before starting treatment between 2006 and 2016. Patients who already had DAH at initial CT imaging were excluded. CT images were evaluated for the presence of ILD and airway disease. The association between preexisting lung involvements and the development of DAH was assessed using logistic regression models adjusted for various clinical characteristics.Results: We identified 113 patients (median age 72 years; median follow-up duration 39 months), and 27 (24%) of them developed DAH during the follow-up. Airway disease was identified in 41 (36%) patients and was independently associated with the development of DAH (adjusted odds ratio 6.86, 95% confidence interval 1.85–25.4). However, ILD identified in 45 (40%) patients was not associated with DAH.Conclusion: Our findings suggest that DAH in MPA occurs frequently in patients with airway disease. Attention to preexisting airway disease may help predict the development of DAH.

Effect of Biological Disease-modifying Anti-rheumatic Drugs on Airway and Interstitial Lung Disease in Patients with Rheumatoid Arthritis

Objective Biological disease-modifying anti-rheumatic drugs (bDMARDs) represent an important advance in alleviating rheumatoid arthritis (RA), but their effect on rheumatic airway disease (AD) and interstitial lung disease (ILD) is still unclear. This study was performed to evaluate the association of the use of different bDMARDs with new-onset or worsening of RA-AD/ILD. Methods We performed a retrospective cohort study of RA patients who received bDMARDs and assessed their AD/ILD before and after drug initiation in our hospital over the past 10 years. We evaluated the serial changes in computed tomography (CT), classified patients according to AD/ILD progression, and analyzed associations between clinical characteristics and outcomes. Results We enrolled 49 patients. Thirty patients received tumor necrosis factor inhibitors (TNFis), 12 received abatacept (ABT), and the remaining 7 received tocilizumab (TCZ). Seventeen patients had ILD, 10 had AD, and 6 had both AD and ILD before the initiation of bDMARDs. New emergence or exacerbation of AD/ILD was observed in 18 patients after drug initiation, while the remaining 31 remained stable or improved. Multiple logistic regression analyses revealed that pre-existing AD was an independent risk factor against the emergence or exacerbation of RA-AD/ILD, and ABT use was a protective factor against it. Conclusion Our study showed that pre-existing RA-AD is associated with future worsening of RA-AD/ILD, and ABT over other bDMARDs was associated with a better prognosis. Future studies to confirm our results are needed.

Small molecule targeting of the STAT5/6 Src homology 2 (SH2) domains to inhibit allergic airway disease

Asthma is a chronic inflammatory disease of the lungs and airways and one of the most burdensome of all chronic maladies. Previous studies have established that expression of experimental and human asthma requires the IL-4/IL-13/IL-4 receptor α (IL-4Rα) signaling pathway, which activates the transcription factor STAT6. However, no small molecules targeting this important pathway are currently in clinical development. To this end, using a preclinical asthma model, we sought to develop and test a small-molecule inhibitor of the Src homology 2 domains in mouse and human STAT6. We previously developed multiple peptidomimetic compounds on the basis of blocking the docking site of STAT6 to IL-4Rα and phosphorylation of Tyr641 in STAT6. Here, we expanded the scope of our initial in vitro structure-activity relationship studies to include central and C-terminal analogs of these peptides to develop a lead compound, PM-43I. Conducting initial dose range, toxicity, and pharmacokinetic experiments with PM-43I, we found that it potently inhibits both STAT5- and STAT6-dependent allergic airway disease in mice. Moreover, PM-43I reversed preexisting allergic airway disease in mice with a minimum ED50 of 0.25 μg/kg. Of note, PM-43I was efficiently cleared through the kidneys with no long-term toxicity. We conclude that PM-43I represents the first of a class of small molecules that may be suitable for further clinical development against asthma.

Air pollution in India and related adverse respiratory health effects: past, present, and future directions.

The review describes current status of air pollution in India, summarizes recent research on adverse health effects of ambient and household air pollution, and outlines the ongoing efforts and future actions required to improve air quality and reduce morbidity and mortality because of air pollution in India. Global burden of disease data analysis reveals more than one million premature deaths attributable to ambient air pollution in 2015 in India. More than one million additional deaths can be attributed to household air pollution. Particulate matter with diameter 2.5 μm or less has been causatively linked with most premature deaths. Acute respiratory tract infections, asthma, chronic obstructive pulmonary disease, exacerbations of preexisting obstructive airway disease and lung cancer are proven adverse respiratory effects of air pollution. Targeting air quality standards laid by WHO can significantly reduce morbidity and mortality because of air pollution in India. India is currently exposed to high levels of ambient and household air pollutants. Respiratory adverse effects of air pollution are significant contributors to morbidity and premature mortality in India. Substantial efforts are being made at legislative, administrative, and community levels to improve air quality. However, much more needs to be done to change the 'status quo' and attain the target air quality standards. VIDEO ABSTRACT: http://links.lww.com/COPM/A24.

Common Transcriptomic Changes Regulated by Innate Immune Receptors and Nuclear Factor NF-kappa-B in Mice Exposed to Ozone

Ozone (O3) is a predominant oxidant in air pollution and has been linked to diminished lung function, respiratory inflammation, and worsening of preexisting airway diseases. Tumor necrosis factor (TNF)-α and toll-like receptor 4 (TLR4) play critical roles in innate immune responses. Signaling through TNF receptor (TNFR) and TLR4 activates nuclear factor NF-kappa-B (NF-κB), leading to the transcriptional regulation of immunity genes. The injurious roles of TNF-α, TLR4, and NF-κB in O3-induced lung pathogenesis have been determined in mice. The current study was designed to examine lung transcriptome changes and downstream mechanisms regulated by these innate immune response factors. Mice lacking Tnfr (Tnfr-/-) or Nfkb (Nfkb-/-), Tlr4 mutant mice (C3H/HeJ), and their wild-types (Tnfr+/+, Nfkb+/+, C3H/HeOuJ) were exposed to air or 0.3 ppm O3. Lung RNAs were isolated for cDNA microarray analysis. Significantly varied genes between the wild-type and gene knockout mice after O3 exposure were determined (2-way ANOVA) to elucidate commonly changed genes between the TNFR-NF-κB, TLR4-NF-κB, and TNFR-TLR4 pathways (Venn Diagram analysis). Downstream mechanisms affected by the common differentially regulated genes and chemicals/drugs that may act on O3-responsive genes were predicted by bioinformatics analysis tools. qPCR, ELISA, Western blotting, and chromatin immunoprecipitation assay validated the results. Tnfr- and Nfkb-dependently changed genes by O3, including matrix metalloproteinase 9 (Mmp9) and endothelin 1 (Edn1), were involved in cell death, connective tissue injury, and inflammation. Interleukin 12 (IL-12) and transforming growth factor (TGF)-β1 were suggested as upstream regulators. Genes changed in common by Tlr4 and Nfkb during O3 exposure (e.g. D-box binding PAR BZIP transcription factor, Dbp; lipocalin 2, Lcn2; serum amyloid A 3, Saa3) were related to lipid derangement, cell morphology, and lymphoid tissue hyperplasia. Common gene transcripts regulated by TNFR and TLR4 such as fatty acid binding protein 1 (Fabp1) and tissue inhibitor of metalloproteinase 1 (Timp1) contributed to the chemotaxis and fatty acid metabolism. In conclusion, the TNFR-NF-κB and TLR4-NF-κB pathways modulated distinct transcriptomes during the development of O3-induced lung injury in mice. Results will provide significant insights into the pulmonary O3 pathogenesis and therapeutic interventions.

Local Effects on Airway Inflammation and Systemic Uptake of 5 nm PEGylated and Citrated Gold Nanoparticles in Asthmatic Mice.

Nanotechnology is showing promise in many medical applications such as drug delivery and hyperthermia. Nanoparticles administered to the respiratory tract cause local reactions and cross the blood-air barrier, thereby providing a means for easy systemic administration but also a potential source of toxicity. Little is known about how these effects are influenced by preexisting airway diseases such as asthma. Here, BALB/c mice are treated according to the ovalbumin (OVA) asthma protocol to promote allergic airway inflammation. Dispersions of polyethylene-glycol-coated (PEGylated) and citrate/tannic-acid-coated (citrated) 5 nm gold nanoparticles are applied intranasally to asthma and control groups, and (i) airway resistance and (ii) local tissue effects are measured as primary endpoints. Further, nanoparticle uptake into extrapulmonary organs is quantified by inductively coupled plasma mass spectrometry. The asthmatic precondition increases nanoparticle uptake. Moreover, systemic uptake is higher for PEGylated gold nanoparticles compared to citrated nanoparticles. Nanoparticles inhibit both inflammatory infiltrates and airway hyperreactivity, especially citrated gold nanoparticles. Although the antiinflammatory effects of gold nanoparticles might be of therapeutic benefit, systemic uptake and consequent adverse effects must be considered when designing and testing nanoparticle-based asthma therapies.

Respiratory Syncytial Virus: Infection, Detection, and New Options for Prevention and Treatment.

Respiratory syncytial virus (RSV) infection is a significant cause of hospitalization of children in North America and one of the leading causes of death of infants less than 1 year of age worldwide, second only to malaria. Despite its global impact on human health, there are relatively few therapeutic options available to prevent or treat RSV infection. Paradoxically, there is a very large volume of information that is constantly being refined on RSV replication, the mechanisms of RSV-induced pathology, and community transmission. Compounding the burden of acute RSV infections is the exacerbation of preexisting chronic airway diseases and the chronic sequelae of RSV infection. A mechanistic link is even starting to emerge between asthma and those who suffer severe RSV infection early in childhood. In this article, we discuss developments in the understanding of RSV replication, pathogenesis, diagnostics, and therapeutics. We attempt to reconcile the large body of information on RSV and why after many clinical trials there is still no efficacious RSV vaccine and few therapeutics.

Air pollution and health

The detrimental health effects of air pollution have always attracted intense interest among researchers from around the world. In 2010, WHO estimated that more than 6 million people die prematurely every year because of air pollution. 1 Lim SS Vos T Flaxman AD et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012; 380: 2224-2260 Summary Full Text Full Text PDF PubMed Scopus (8390) Google Scholar Both ambient air pollution and indoor air pollution have been linked to various adverse health outcomes, especially in people with pre-existing medical conditions. Although it might seem obvious that air pollution can affect people with pre-existing airway diseases, there are few controlled human exposure studies that can provide irrefutable evidence of adverse effects after acute exposure to an individual pollutant. 2 Brunekreef B Holgate ST Air pollution and health. Lancet. 2002; 360: 1233-1242 Summary Full Text Full Text PDF PubMed Scopus (2957) Google Scholar Such controlled human exposure studies might also enable a better understanding of the underlying mechanisms leading to possible adverse outcomes. 3 Rom WN Boushey H Caplan A Experimental human exposure to air pollutants is essential to understand adverse health effects. Am J Respir Cell Mol Biol. 2013; 49: 691-696 Crossref PubMed Scopus (22) Google Scholar Ambient air contains many pollutants including gases such as ozone, oxides of nitrogen, and sulphur dioxide along with particulates of different sizes. Because of the complexity of the composition of air pollutants and the difficulty of precisely measuring exposure, identifying the role of different pollutants in respiratory morbidity is no simple task. Quantification of pollutant exposure in a study population is imprecise, because the levels of different components might vary with time and with the surroundings of the studied participants. Despite these difficulties, there have been several important reports published in 2013 that improve our understanding of the adverse health effects of air pollution.

Allergic Airway Disease in Mice Alters T and B Cell Responses during an Acute Respiratory Poxvirus Infection

Pulmonary viral infections can exacerbate or trigger the development of allergic airway diseases via multiple mechanisms depending upon the infectious agent. Respiratory vaccinia virus transmission is well established, yet the effects of allergic airway disease on the host response to intra-pulmonary vaccinia virus infection remain poorly defined. As shown here BALB/c mice with preexisting airway disease infected with vaccinia virus developed more severe pulmonary inflammation, higher lung virus titers and greater weight loss compared with mice inoculated with virus alone. This enhanced viremia was observed despite increased pulmonary recruitment of CD8+ T effectors, greater IFNγ production in the lung, and high serum levels of anti-viral antibodies. Notably, flow cytometric analyses of lung CD8+ T cells revealed a shift in the hierarchy of immunodominant viral epitopes in virus inoculated mice with allergic airway disease compared to mice treated with virus only. Pulmonary IL-10 production by T cells and antigen presenting cells was detected following virus inoculation of animals and increased dramatically in allergic mice exposed to virus. IL-10 modulation of host responses to this respiratory virus infection was greatly influenced by the localized pulmonary microenvironment. Thus, blocking IL-10 signaling in virus-infected mice with allergic airway disease enhanced pulmonary CD4+ T cell production of IFNγ and increased serum anti-viral IgG1 levels. In contrast, pulmonary IFNγ and virus-specific IgG1 levels were reduced in vaccinia virus-treated mice with IL-10 receptor blockade. These observations demonstrate that pre-existing allergic lung disease alters the quality and magnitude of immune responses to respiratory poxviruses through an IL-10-dependent mechanism.

Effects of inhaled corticosteroids on voice production in healthy adults

The isolated effects of inhaled corticosteroids (ICS) on voice production were examined in 30 healthy adults with no known pre-existing airway disease. All participants followed a daily ICS treatment regime of 500 μg in the morning and evening over a 6-day period. Sustained vowels and connected speech samples were audio recorded before, during, and after the ICS regime. Each participant's audio recorded samples were acoustically analysed. Results revealed that ICS has a short-term detrimental effect on various acoustic properties of voice. These effects were more evident in connected speech compared to isolated vowel productions. All acoustic parameters returned to normalcy after discontinuing the ICS. The study provides insight as to the influence of ICS on healthy voice production.

Year in review 2012: Lung cancer, respiratory infections, tuberculosis, pleural diseases, bronchoscopic intervention and imaging

This Year in Review series addresses the most relevant articles published in Respirology and other respiratory medicine journals during 2012 concerning five specific areas that we consider to be of importance to practicing pulmonologists, namely lung cancer, respiratory infections, tuberculosis (TB), pleural diseases, and interventional pulmonology and imaging. Some important findings that will be commented on more in depth are that: 1) screening for lung cancer using low-dose computed tomography (CT) in high risk populations is promising, although not firmly established, 2) an enhanced CURB (which stands for confusion, urea, respiratory rate, blood pressure) score as well as the Japanese A-DROP (age, dehydration, respiratory failure, orientation disturbance, and pressure) prognostic scale are as accurate as the pneumonia severity index (PSI) scoring system to predict mortality in patients with community-acquired pneumonia (CAP), 3) randomized trials are urgently needed to optimize multidrug-resistant (MDR)-TB treatment, 4) the use of video-assisted thoracoscopic surgery (VATS) to quantify pleural tumor burden and, if feasible, perform an intrathoracic cytoreduction in patients with malignant effusions secondary to ovarian cancer (OC) may have a significant impact on further patient management plans, and 5) respiratory endoscopy and its different diagnostic and therapeutic modalities, is a safe procedure with overall complication rates less than 1%.

Effects of obesity and weight loss on airway physiology and inflammation in asthma

Obesity is a major risk factor for asthma, but the mechanisms for the development of asthma in the setting of obesity are not known. The purpose of this article is to review the effects of obesity on airway inflammation in patients with asthma, and to discuss the effects of obesity on airway reactivity in patients with asthma.Obesity is particularly a risk factor for non-atopic asthma. Airway eosinophilic inflammation is not increased in obesity, in fact the preponderance of the evidence suggests that airway eosinophilia is decreased in obesity. There is some preliminary data suggesting that airway neutrophilia may be increased in obesity, and that this may be particularly related to dietary fats. Obesity also alters adaptive immunity, and may suppress lymphocyte function typically associated with asthmatic airway inflammation.Population based studies are somewhat inconsistent on the relationship between airway reactivity and asthma, however, recent studies in bariatric surgery show that weight loss surgery in severely obese patients decreases airway reactivity. One study suggested that this was particularly the case for those with low IgE (a marker of a low TH2 asthma phenotype), suggesting there may be some heterogeneity in asthma in obesity.There are likely to be two phenotypes of asthma in the obese: one group with early onset disease and asthma complicated by obesity, and a 2nd group with late onset disease with asthma consequent to obesity. Obesity leads to profound changes in airway function, and adaptive and innate immune responses which alter the nature of pre-existing allergic airway disease, and also cause new onset asthmatic disease.

Repeated exposure to aerosolized brevetoxin-3 induces prolonged airway hyperresponsiveness and lung inflammation in sheep

Context: During a Florida red tide, brevetoxins (PbTxs) produced by Karenia brevis become aerosolized and can cause both immediate and prolonged airway symptoms in humans, especially in those with preexisting airway disease (e.g., asthma). Although environmental monitoring indicates that toxins remain airborne for up to 4 consecutive days, there is little information on airway responses after multiple-day exposures.Objectives: To delineate putative mechanisms leading to pulmonary dysfunction after PbTx exposure, we studied airway responses before and after multiple exposures to aerosol PbTx-3, the most potent PbTx produced, in nonallergic (healthy) and in allergic sheep, which serve as a surrogate for patients with compromised airways.Methods: Both groups were exposed to 20 breaths of increasing concentrations of PbTx-3 (30–300 pg/mL) for 4 consecutive days. Airway responsiveness to carbachol (1 and 8 days after) and airway inflammation as assessed by bronchoalveolar lavage (0 and 7 days after) were measured.Results: Both groups developed airway hyperresponsiveness (AHR) 1 day after challenge; the severity was concentration dependent and more severe in the allergic group. AHR remained after 8 days, but the difference in the severity between the groups was lost. Both groups developed an inflammatory response after exposure to 300 pg/mL PbTx-3. Immediately after exposure, lung neutrophilia was prominent. This neutrophilia persisted for 7 days in addition to increases in total cells and macrophages.Conclusion: Repeated exposures to PbTx-3 result in prolonged AHR and lung inflammation. These pathophysiologic responses could be underlying contributors to the prolonged respiratory symptoms in humans after red tides.