A better futureHill; Inhaled corticosteroids and risk of pneumonia: Inhaled corticosteroids Inhalde are commonly used in the treatment of chronic obstructive pulmonary disease. Recent large prospective trials have reported an increased incidence of pneumonia in patients treated with ICS. Despite this, the link between ICS and pneumonia remains controversial. In this review, pro and con arguments for the association between ICS and increased pneumonia inhaled corticosteroids for pneumonia are discussed, drawing on evidence from experimental anavar hi tech dosis clinical research.
Inhaled Steroids Tied to Increased Pneumonia Risk in Asthma Patients | Medpage Today
Hill; Inhaled corticosteroids and risk of pneumonia: Inhaled corticosteroids ICS are commonly used in the treatment of chronic obstructive pulmonary disease. Recent large prospective trials have reported an increased incidence of pneumonia in patients treated with ICS. Despite this, the link between ICS and pneumonia remains controversial. In this review, pro and con arguments for the association between ICS and increased pneumonia risk are discussed, drawing on evidence from experimental and clinical research.
Recent large prospective trials have reported an increased incidence of pneumonia in patients with COPD taking ICS that has raised concern about their use. This potential association is important because patients with COPD who develop pneumonia may experience worse clinical outcomes. The aim of this review is to discuss pro and con arguments for the association between ICS and increased pneumonia risk, drawing on evidence from experimental and clinical research.
There are no experimental studies specifically designed to examine the pathophysiological processes underlying this proposed association but some of the existing knowledge on mechanisms of corticosteroid action offers potential putative mechanisms. However, such mechanisms are poorly understood and studies in vitro and in animal models are required for further characterization.
The majority of clinical evidence for the association between use of ICS and increased pneumonia risk has come from large randomized controlled trials RCTs. The three largest trials, which have reported an increase in risk of pneumonia, have compared fluticasone alone or in combination with salmeterol with placebo or other inhaled therapies and have reported an increased frequency of pneumonia in fluticasone-containing treatment arms alone or in combination.
Two recent meta-analyses that have included the above trials and other smaller studies in the literature have both concluded that ICS therapy is significantly associated with increased risk of pneumonia.
Supportive evidence also exists from studies with other methodological designs other than randomized clinical trials. A Canadian population-based cohort study used a nested case—control analysis to investigate effect of ICS use on risk of hospitalization for pneumonia. There was no difference in all-cause mortality between patients on ICS and those who were not. The additional strength of this study was that, unlike the clinical trials described above, pneumonia risk was the specific predefined endpoint.
The large body of evidence from studies of different design, in different populations, offers strong support that ICS are associated with increased risk of pneumonia. Studies using respiratory epithelial cell cultures have indicated that pre-incubation of tissue from normal subjects with fluticasone propionate causes a significant reduction in invasion of epithelial cells by common bacterial pathogens such as Pseudomonas aeruginosa , 32 S. Animal studies have also shown that treating mice with inhaled fluticasone propionate significantly reduces invasion of Mycoplasma pneumoniae in lung tissue and suppresses lung inflammation.
In contrast, results from these experimental studies suggest that ICS therapy would be expected to reduce the risk of bacterial infection and pneumonia and thus do not provide a convincing mechanistic explanation for the proposed association.
Evidence suggests that diagnosis of pneumonia based on clinical symptoms and signs alone is unreliable 35 and since the clinical presentation of COPD exacerbation and pneumonia may overlap considerably, without radiographic confirmation, an adverse event could potentially be misclassified as pneumonia rather than exacerbation and vice versa.
This raises doubt over whether a true increase in pneumonia has been observed in these trials. Future prospective RCTs of inhaled corticosteroids with a prespecified outcome of development of pneumonia, using objective criteria including radiographic confirmation are now needed to provide further clarification.
Another potential confounding factor, which may cast doubt over whether a true increased pneumonia risk exists is the use of antibiotics in the treatment and control groups in these studies.
Since the control groups in these studies had significantly more frequent exacerbations than the ICS groups, they may have received more courses of antibiotics. Although this was not the case in one trial, 6 where antibiotics were actually shown to be more frequently prescribed in the ICS arm, it is unclear from the data presented by other trials 5 and antibiotic usage is not a factor that is controlled for in any of the existing meta-analyses.
Bacterial load is known to correlate with airways inflammation 36 and treatment with antibiotics has been shown to reduce bacterial load in patients with COPD.
Future studies and meta-analyses should adjust for antibiotic usage, to characterize this further. Despite ICS use being associated with increased pneumonia risk in these trials, there has not been a reported increase in overall mortality in any of the clinical trials.
This may be considered by some to be an unexpected finding, on the basis of studies, which suggest that patients with COPD who are hospitalized with pneumonia have higher mortality rates than those without COPD, 8—10 although others have shown the opposite and this remains a controversial area.
There have been some suggestions that the risk of pneumonia with ICS may be dose dependent or related to only certain classes of ICS. Differences exist in the pharmacological actions and metabolism of different ICS, with budesonide being more rapidly cleared from airways than higher potency ICS such as fluticasone.
This contrasts with the results of two other meta-analyses that did not separate out class or strength of ICS when considering studies for inclusion and were more heavily influenced by studies using fluticasone. Several population-based studies have identified risk factors for development of CAP, and although many have found a history of COPD to be an independent risk factor for development of CAP, 45,46 very few have separated out the influence of treatments to examine whether ICS use is an independent risk factor.
A large Spanish study of patients with confirmed CAP showed that use of ICS was associated with CAP in bivariate analysis but was not independently associated after adjustment on multivariate analysis. The advantage of this study is that all patients included had radiologically confirmed pneumonia, thus eliminating the possibility of clinical overlap with COPD exacerbations.
However, the fact that this study did not find ICS use to be an independent risk factor for pneumonia goes against the proposed association. Although several clinical trials have reported increased pneumonia risk with ICS, there are problems with the reliability of this conclusion, largely due to the fact that none of the trials were specifically designed to assess this outcome. This issue will remain unresolved, until a large prospective trial is conducted, which uses objective criteria for definition of pneumonia.
Furthermore, studies using ICS in vitro and in animal models do not support an association with increased pneumonia and suggest that ICS should reduce bacterial invasion into lung tissue. To date, the link between ICS therapy in COPD and increased pneumonia risk is unclear and evidence from experimental and clinical studies discussed above is conflicting.
Table 3 summarizes evidence for and against the proposed association. Further experimental and clinical studies are needed. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account.
Close mobile search navigation Article navigation. Evidence for the association of ICS with increased risk of pneumonia. Evidence against the association of ICS with increased risk of pneumonia. Inhaled corticosteroids and risk of pneumonia: Abstract Inhaled corticosteroids ICS are commonly used in the treatment of chronic obstructive pulmonary disease.
Forced expiratory volume in first second; Exac: Evidence for and against association of ICS and pneumonia from experimental and clinical studies. Several large prospective trials report increased pneumonia associated with ICS use. ICS not identified as an independent risk factor for pneumonia in a population based study. Analysis of inhaled corticosteroid and oral theophylline use among patients with stable COPD from to Prevalence of inhaled corticosteroid use among patients with chronic obstructive pulmonary disease.
Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease: Standards for the diagnosis and treatment of patients with COPD: Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. Implications of COPD in patients admitted to the intensive care unit by community-acquired pneumonia. COPD is associated with increased mortality in patients with community-acquired pneumonia.
Targeting the NF-kB pathway in asthma and chronic obstructive pulmonary disease. New insights into the role of nuclear factor-kB, a ubiquitous transcription factor in the initiation of diseases. Mapping of glucocorticoid receptor DNA domain surfaces contributing to transrepression of NF-kappa B and induction of apoptosis. Physical association and functional antagonism between the p65 subunit of transcription factor NF-kB and the glucocorticoid receptor.
Characterisation of the mechanisms involved in transrepression of NF-kB by activated glucocorticoid receptors. Increased expression of nuclear factor-kappaB in bronchial biopsies from smokers and patients with COPD. Role of deficient type III interferon-lambda production in asthma exacerbations. Toll-like receptor 2 plays a role in the early inflammatory response to murine pneumococcal pneumonia but does not contribute to the antibacterial defense.
Recognition of pneumolysin by Toll-like receptor 4 confers resistance to pneumococcal infection. Pneumococcal cell wall activates NF-kB in human Monocytes: Nuclear factor-kappaB activation in mouse lung lavage cells in response to Streptococcus pneumoniae pulmonary infection.
Targeted disruption of the p5- subunit of NF-kappa B leads to multifocal defects in immune responses. Inhaled corticosteroids in patients with stable chronic-obstructive pulmonary disease. A Systematic review and meta-analysis. Long term use of inhaled corticosteroids and the risk of pneumonia in Chronic-obstructive pulmonary disease.
Inhaled corticosteroid use in chronic obstructive pulmonary disease and the risk of hospitalisation for pneumonia. Effect of fluticasone propionate and salmeterol on Pseudomonas aeruginosa infection of the respiratory mucosa in vitro. Inhaled fluticasone propionate reduces concentration of Mycoplasma pneumoniae, inflammation and bronchial hyperresponsiveness in lungs of mice. Does this patient have community-acquired pneumonia? Diagnosing pneumonia by history and physical examination.
Association between airway bacterial load and markers of airway inflammation in patients with stable chronic bronchitis. Resolution of bronchial inflammation is related to bacterial eradication following treatment of exacerbations of chronic bronchitis. Mortality in COPD patients with community-acquired pneumonia: Pneumonia in the patient with chronic obstructive pulmonary disease.
Levels of severity and risk classification. Inhaled corticosteroids do not reduce mortality but increase pneumonia in COPD. Pneumonia risk in COPD patient receiving inhaled corticosteroids alone or in combination: Plasma concentrations of fluticasone propionate and budesonide following inhalation: Budesonide and the risk of pneumonia: Risk factors fro community-acquired pneumonia in adults: Risk factors for community-acquired pneumonia diagnosed by general practitioners in the community.
New evidence of risk factors for community-acquired pneumonia: For Permissions, please email: Email alerts New issue alert. Receive exclusive offers and updates from Oxford Academic. Inhaled corticosteroids and the risk of fracture in chronic obstructive pulmonary disease.