Casalini and Ian M. The T lymphocyte-mediated immune response to Mycobacterium tuberculosis infection in the parietal pleura of patients with tuberculous pleurisy is unknown. The aim of this study was to investigate the immune response in the parietal pleura of tuberculous pleurisy compared with nonspecific pleuritis.
There was no significant difference between the two groups of subjects in the number of CD8, CD68, neutrophil elastase. Documents: Advanced Search Include Citations.
Authors: Advanced Search Include Citations. CasaliniIan M.
Transcription factors in asthma and COPD
BarnesAlberto Papi. Abstract The T lymphocyte-mediated immune response to Mycobacterium tuberculosis infection in the parietal pleura of patients with tuberculous pleurisy is unknown. Keyphrases tuberculous pleurisy parietal pleura immune response mycobacterium tuberculosis infection nonspecific pleuritis subject control group nonspecific pleuritis receiver operator toluidine blue cell inflammatory cell th1 th2 th17 treg cell ccr4 cell logistic regression tryptase cell significant difference neutrophil elastase single marker rorc2 mrna gata-3 cell t-cell subset lymphocyte-mediated immune response tuberculous pleurisy patient.
Powered by:.The immunopathology of chronic obstructive pulmonary disease COPD is based on the innate and adaptive inflammatory immune responses to the chronic inhalation of cigarette smoking. This also has provided a scientific rationale for new drugs discovery and targeting to the lower airways.
This review summarises and discusses the immunopathology of COPD patients, of different severity, compared with control smokers with normal lung function.
Role of transcription factors in the pathogenesis of asthma and COPD
Chronic obstructive pulmonary disease COPD is the 3rd leading cause of morbidity and mortality worldwide [ 1 ]. The etiology of COPD is due to complex interactions between environmental factors particularly cigarette smoking and genetic factors. The cigarette smoke activates macrophages, dendritic cells and airway epithelial cells in response to toxic particles in the smoke.
The inflammatory process also mediates small airway fibrosis. The activation of these and other cell types and the activation of inflammatory and remodelling processes lead to small airway fibrosis, obstructive bronchiolitis, pulmonary emphysema and mucus hypersecretion.
COPD pathology in the small airways
There are, so far, very few studies comparing the pathology between cigarette-smoking-associated COPD and other causes of disease [ 56 ]; for this reason, our review of the literature will be limited to the immunopathology in cigarette-smoking-associated COPD.
The progressive chronic airflow limitation in COPD is due to two major pathological processes: remodelling and narrowing of small airways and destruction of the lung parenchyma with consequent loss of the alveolar attachments of these airways as a result of pulmonary emphysema. This results in diminished lung recoil, higher resistance to flow and closure of small airways at higher lung volumes during expiration, with consequent air trapping in the lung.
This leads to the characteristic hyperinflation of the lungs, which gives rise to the sensation of dyspnea and decrease exercise tolerance [ 7 ]. Both the small-airway remodelling and narrowing and the pulmonary emphysema are likely to be the results of chronic inflammation in the lung periphery [ 8 ].
The major site of increased resistance is localised to the small airways less than 2 mm in internal diameter, which are located from the 4th to the 12th generation of airway branching in the lung] [ 9 — 11 ] and was confirmed using 3-D computed tomography [ 12 ]. Bronchioles differ from bronchi by having no cartilage and submucosal glands, a relatively greater proportion of smooth muscle and fewer mucus-secreting cells in the epithelial layer.
The chronic airflow obstruction in smoking-induced COPD results from a combination of small-airway inflammation and remodelling and loss of lung elasticity due to lung parenchymal destruction.
Although pulmonary emphysema usually only appears with increasing disease severity, it can also occur in subjects without airflow obstruction [ 1719 — 21 ]. Lesions in the small airways are a major determinant of COPD progression and severity, and there is a strong inverse association between total small airway wall thickness and FEV 1 [ 8 ]. Lower airways and lung inflammation in stable COPD patients is characterised by increased numbers of macrophages, neutrophils, T and B lymphocytes and dendritic cells Fig.
However, the predominant inflammatory cell type varies with disease severity; increased numbers of neutrophils and B lymphocytes are present in the most severe grades III and IV disease [ 816 — 18 ].
The functional role of these inflammatory cells, including their subsets, is still largely unknown but the interaction between lymphocytes and macrophages may orchestrate the onset, progression and severity of lower airways inflammation and there is mounting evidence that innate immunity, but not inflammasome activation, correlates with the progression of the severity of stable COPD [ 22 ].
Representative immunohistochemical staining for CD68 DAB ; brown of alveolar macrophages ab and for neutrophil elastase alkaline phosphatase, red cd in paraffin sections of the small airways of stable moderate COPD patients bd and of control smokers with normal lung function ac.
In smokers, the development of airflow obstruction is associated with more pronounced small-airway inflammation and appearance of increased thickness of their wall due to fibrosis and smooth muscle hypertrophy [ 151718 ].
There is a regional distribution of the inflammatory process in the small airways of patients with COPD. Hogg and colleagues assessed the small airways inner diameter less of 2 mm in surgically resected lung tissue from patients 39 with stage 0 smokers with normal lung function and chronic bronchitis39 with stage 1 mild22 with stage 2 moderate16 with stage 3 severe and 43 with stage 4 very severe COPD, according to the GOLD classification [ 1811 ].
This study clearly demonstrated that lesions in the small airways are a major determinant of the progression and severity of COPD. Progression of COPD is also associated with the accumulation of inflammatory mucous exudates in the lumen and infiltration of the wall by innate and adaptive inflammatory immune cells that form lymphoid follicles [ 811 ]. For this reason, the inflammatory response present in the small airways of the patients with stable COPD is considered an amplification of the inflammatory response to irritants that is seen in smokers with normal lung function [ 1024 ].
These data suggest that the T lymphocyte increases may be an effect of smoking [ 29 ]. Mature T cells have a greater propensity to cause tissue damage [ 31 ]. Arrows indicate the positively stained cells.
These data highlight the importance of activation status over cell presence.To browse Academia. Skip to main content.
Log In Sign Up. Add Social Profiles Facebook, Twitter, etc. Unfollow Follow Unblock. Other Affiliations:. Chronic obstructive pulmonary disease international guidelines more. Although chronic obstructive pulmonary disease COPD has a public health importance similar to asthma, it has received less attention. In the Canadian Thoracic Society released its guidelines. All these documents were followed in by the guidelines developed by the British Thoracic Society.
These COPD guidelines show many similarities but also have some interesting differences. The aim of this paper is to review these similarities and discrepancies.
Like all guidelines, COPD guidelines suffer from the limited amount of evidence-based medicine supporting them, a limitation that, however, provides a strong stimulus for further research. Pathogenic link between chronic obstructive pulmonary disease and squamous cell lung cancer more.
Expert Rev Respir Med. Pathogenic link between chronic obstructive pulmonary disease and squamous cell lung cancer. Caramori G, Papi A.
Publication Types: Editorial. Public health systems and services research. Similarities and discrepancies between exacerbations of asthma and chronic obstructive pulmonary disease more. Publication Date: Publication Name: Thorax. Decreased T lymphocyte infiltration in bronchial biopsies of subjects with severe chronic obstructive pulmonary disease more. Remember me on this computer. Enter the email address you signed up with and we'll email you a reset link.
Need an account? Click here to sign up.The global COVID pandemic has led to a race to find medications that can improve the prognosis of the disease.
Azithromycin, in association with hydroxychloroquine or chloroquine, has been proposed as one such medication. The aim of this review is to describe the pharmacological mechanism, clinical evidence and prescribing guidelines concerning azithromycin in COVID patients.
There is weak evidence on the antiviral and immunomodulating effects of azithromycin, which in addition is not based on results from COVID patients specifically. Therefore, this antibacterial should be considered only as empirical treatment of community-acquired pneumonia CAPalthough not all current treatment guidelines are in agreement.
After the initial expectations raised by a small trial, more recent evidence has raised serious safety concerns on the use of hydroxychloroquine or chloroquine with azithromycin to treat COVID patients, as all these drugs have arrhythmogenic potential.
The World Health Organization has not made recommendations suggesting the use of azithromycin with hydroxychloroquine or chloroquine as treatment for COVID, but some national organisations have taken a different position, recommending this as first-line treatment. Several scientific societies, including the American College of Cardiology, have cautioned about the risks of this treatment in view of the lack of evidence concerning its benefits.
The global COVID pandemic has led to 9, infected patients anddeaths worldwide between 31st December and 25th Juneaccording to the European Centre for Disease Control [ 1 ]. This public health emergency has triggered a race to find medications to improve the prognosis of disease. In turn, this has led to a tug of war between proponents of the conservative approach of not using medications in COVID infection unless their risk—benefit profile has been scientifically proven and the proponents of the non-conservative approach proposing to offer new treatment even in absence of strong scientific evidence, on the basis of clinical intuition or in vitro findings only [ 2 ].
Making such decisions under the pressure of a pandemic is not easy. On one hand, scientific evidence is needed to confirm that the benefits of treatment outweigh the risks, but on the other hand, the clinical trials needed to do this can be difficult to plan, implement and ultimately generate robust scientific evidence in a short time.
There is currently great interest in drug repurposing or repositioning to manage COVID infection, that is, the evaluation of the usefulness of a drug for an indication different to that for which it was marketed.
Clinical evidence on the antibacterial effect in community-acquired pneumonia CAP as well as immunomodulating and antiviral actions as a rationale for the use of azithromycin in COVID are reviewed and prescribing guidelines discussed in detail. The strongest evidence of effectiveness for azithromycin concerns its role as an antibacterial drug. Although there is no direct evidence of the effectiveness of azithromycin in COVID, some scientific bodies have suggested that the antibacterial properties of azithromycin remain clinically useful in the empirical treatment of CAP occurring in COVID patients.
Not all current treatment guidelines agree on azithromycin use in CAP. There is weak evidence on the antiviral and immunomodulating effects of azithromycin, which in addition was not derived from persons with COVID specifically. The available evidence is discussed below. In most patients with suspected or confirmed SARS-CoV-2 infection, lung damage correlates with the severity of viral infection; however, bacterial co-infection has been reported in several patients affected by COVID pneumonia [ 567 ].
Thus, some guidelines have been adapted in the context of the COVID pandemic to promote the appropriate use of antibiotics and to delineate the role of these drugs, including azithromycin, in COVID patients. In the absence of bacterial co-infection, antibiotic therapy is contraindicated for COVID pneumonia, because it would be ineffective, considering its viral aetiology.
Therefore, according to NICE the use of antibiotics should be limited only to the management of those situations in which bacterial pulmonary co-infections are suspected or confirmed. The decision-making process in choosing antibiotic therapy should be based on clinical tests, such as microbiological tests, chest imaging, complete blood count, urine tests for legionella and pneumococcal antigens.
Moreover, for the treatment of severe bacterial CAP in COVID patients, the NICE guideline suggests the use of clarithromycin among macrolide antibiotics, in association with co-amoxiclav, orally or intravenously, or in co-administration with cefuroxime as an alternative to co-amoxiclav.
Although, in a systematic review, it was found that the clinical efficacy and number of adverse events of azithromycin was not significantly different from clarithromycin in adults with low- to moderate-severity CAP [ 9 ], azithromycin is not recommended for the treatment of CAP or HAP in the NICE guideline because its long half-life could increase the risk of antibacterial resistance [ 10 ]. Since cytokine release syndrome CRSalso known as cytokine storm, seems to be a major driver of mortality in COVID, several drugs with immunomodulating activity have been proposed as potential agents to be repurposed for the treatment of COVID patients [ 11 ].
Indeed, several immunomodulatory effects of azithromycin have been found in many experimental studies [ 121314 ]. Due to these immunomodulatory effects, azithromycin has proven effective in the management of several chronic lung diseases, such as cystic fibrosis CFnon-CF bronchiectasis, chronic obstructive pulmonary disease, chronic rhinosinusitis, sepsis and diffuse panbronchiolitis [ 1213 ]. Therefore, modulation of the inflammatory response may theoretically reduce the complications of viral pneumonia [ 11 ].
However, the use of immunomodulatory agents, such as corticosteroids, in patients with SARS has not shown significant beneficial effects [ 15 ]. However, very recently announced results from the Oxford University Recovery Trial seem to suggest that dexamethasone reduced mortality among patients receiving invasive mechanical ventilation or oxygen, but not among those not receiving respiratory support [ 16 ].
Azithromycin is also thought to have antiviral properties that may work in synergy with antiviral drugs. Preclinical studies have found that this macrolide antibiotic can exert antiviral effects against Zika virus, rhinovirus and Ebola virus [ 17181920 ].Inflammation is a central feature of asthma and chronic obstructive pulmonary disease COPD and both are characterized by an increased transcription of pro-inflammatory proteins eg, cytokines, chemokines, growth factors and enzymes.
Changes in inflammatory gene transcription are regulated by transcription factors that may therefore play a key role in the pathogenesis of asthma and COPD by amplifying and perpetuating the inflammatory process, and thereby contributing to disease severity and responsiveness to treatment. Several new compounds based on interactions with specific transcription factors or their activation pathways are now in development for the treatment of asthma and COPD.
Abstract Inflammation is a central feature of asthma and chronic obstructive pulmonary disease COPD and both are characterized by an increased transcription of pro-inflammatory proteins eg, cytokines, chemokines, growth factors and enzymes. Publication types Research Support, Non-U. Gov't Review. Substances Transcription Factors.Abstract: Inflammation of the lower airways is a central feature of chronic obstructive pulmonary disease COPD.
Inflammatory responses are associated with an increased expression of a cascade of proteins including cytokines, chemokines, growth factors, enzymes, adhesion molecules and receptors.
In most cases the increased expression of these proteins is the result of enhanced gene transcription: many of these genes are not expressed in normal cells under resting conditions but they are induced in the inflammatory process in a cell-specific manner. Transcription factors regulate the expression of many pro-inflammatory genes and play a key role in the pathogenesis of airway inflammation.
Many studies have suggested a role for viral infections as a causative agent of COPD exacerbations. In this review we will focus our attention on the relationship between common respiratory viral infections and the molecular and inflammatory mechanisms that lead to COPD exacerbation. Documents: Advanced Search Include Citations. Authors: Advanced Search Include Citations.
Abstract Abstract: Inflammation of the lower airways is a central feature of chronic obstructive pulmonary disease COPD. Keyphrases viral-induced exacerbation review pathophysiology copd exacerbation increased expression viral infection adhesion molecule many study common respiratory viral infection cell-specific manner growth factor inflammatory process central feature many pro-inflammatory gene airway inflammation key role transcription factor enhanced gene transcription inflammatory response normal cell causative agent inflammatory mechanism chronic obstructive pulmonary disease.
Powered by:.CHA CHA KING at home in the wet conditions and has outstanding form at this track, cannot be ruled out. DURE goes well in the wet and drawn ideally, don't treat lightly. LOYAL TOAST in strong form with two wins from 11 attempts this campaign and goes down in weight, capable of getting into the money.
Wanna Get a What (4) 4. Dolly's Due (11) 3. Miss Liffey (7) WANNA GET A WHAT a winner at first outing this prep and has shown early speed in races to date, key chance. DOLLY'S DUE has the speed to overcome a very wide draw, place claims. Proven second-up runner winning in two of six attempts and ran second at Sapphire Coast last try second-up, capable of getting into the money.
MISS LIFFEY coming off a win at Wagga Wagga when fresh and likely to race on the speed, strong place chance. Just Favulous (1) 1. Grand de Lago (6) 4. Mishani Ruler (4) 6. Endless Sizzle (2) On pace runners will have an advantage as little speed engaged. JUST FAVULOUS drawn the rails, key chance.
GRAND DE LAGO couldn't hold on and just missed last start at Toowoomba on a soft track, the real danger in the race. MISHANI RULER first starter and untrialled, quinella. ENDLESS SIZZLE ran six lengths back from the winner at only start at Toowoomba on a soft track but drops in weight, needs the breaks. Snuggle Pot (3) 3. Spur With Ease (6) 2.
Jomar Saga (1) 5. Telloff (4) SNUGGLE POT generally races near the speed and all wins have come when faced with dry ground, will take the power of beating. SPUR WITH EASE 2 wins from seven attempts this campaign and finished fifth last start at Roma, outside hope. JOMAR SAGA back after 37 week break and generally strong first-up placing at Toowoomba last attempt, for the exotics. TELLOFF all wins have come when faced with dry ground and won't be far away in the run, for the wider exotics.
Behind the Thistle (1) 9. Mishani Pilgrim (12) 11. Rosie's Tiara (4) BEHIND THE THISTLE on a seven day back-up and drawn ideally, major contender. MISHANI PILGRIM back after 18 week break, place best.
COOLMUNDA ran six lengths back from the winner last start at Sunshine Coast on a soft track when fresh and generally races near the speed, place only. ROSIE'S TIARA finished nine lengths off the winner last start at Toowoomba when resuming and placed at Toowoomba in only second-up attempt, place hope.
Murphy's Hustler (4) 2.