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Fulltext Inflammation and lung injury in an ovine model of fluid resuscitated endotoxemic shock

Passmore MR, Byrne L, Obonyo NG, See Hoe LE, Boon AC, Diab SD, et al.

Respir Res, 2018 Nov 22;19(1):231.
PMID: 30466423 DOI: 10.1186/s12931-018-0935-4

BACKGROUND: Sepsis is a multi-system syndrome that remains the leading cause of mortality and critical illness worldwide, with hemodynamic support being one of the cornerstones of the acute management of sepsis. We used an ovine model of endotoxemic shock to determine if 0.9% saline resuscitation contributes to lung inflammation and injury in acute respiratory distress syndrome, which is a common complication of sepsis, and investigated the potential role of matrix metalloproteinases in this process.
METHODS: Endotoxemic shock was induced in sheep by administration of an escalating dose of lipopolysaccharide, after which they subsequently received either no fluid bolus resuscitation or a 0.9% saline bolus. Lung tissue, bronchoalveolar fluid (BAL) and plasma were analysed by real-time PCR, ELISA, flow cytometry and immunohistochemical staining to assess inflammatory cells, cytokines, hyaluronan and matrix metalloproteinases.
RESULTS: Endotoxemia was associated with decreased serum albumin and total protein levels, with activated neutrophils, while the glycocalyx glycosaminoglycan hyaluronan was significantly increased in BAL. Quantitative real-time PCR studies showed higher expression of IL-6 and IL-8 with saline resuscitation but no difference in matrix metalloproteinase expression. BAL and tissue homogenate levels of IL-6, IL-8 and IL-1β were elevated.
CONCLUSIONS: This data shows that the inflammatory response is enhanced when a host with endotoxemia is resuscitated with saline, with a comparatively higher release of inflammatory cytokines and endothelial/glycocalyx damage, but no change in matrix metalloproteinase levels.
Fulltext It is time to change the way we manage mild asthma: an update in GINA 2019

Muneswarao J, Hassali MA, Ibrahim B, Saini B, Ali IAH, Verma AK

Respir Res, 2019 Aug 14;20(1):183.
PMID: 31412856 DOI: 10.1186/s12931-019-1159-y

Asthma is a heterogeneous lung disease, usually characterised by chronic airway inflammation. Although evidence-based treatments are available in most countries, asthma control remains suboptimal, and asthma-related deaths continue to be an ongoing concern. Generally, it is believed that between 50 to 75% of patients with asthma can be considered as having mild asthma.Previous versions of Global Initiative for Asthma (GINA) suggested that mild asthma in adults can be well managed with either reliever medications, for example, short-acting beta2 agonists (SABA) alone or with the additional use of controllers such as regular low-dose inhaled corticosteroids (ICS). Given the low frequency or non-bothersome nature of symptoms in mild asthma, patients' adherence towards their controller medications, especially to ICS is usually not satisfactory. Such patients often rely on SABA alone to relieve symptoms, which may contribute to SABA over-reliance. Overuse of relievers such as SABAs has been associated with poor asthma outcomes, such as exacerbations and even deaths. The new GINA 2019 asthma treatment recommendations represent significant shifts in asthma management at Steps 1 and 2 of the 5 treatment steps. The report acknowledges an emerging body of evidence suggesting the non-safety of SABAs overuse in the absence of concomitant controller medications, therefore does not support SABA-only therapy in mild asthma and has included new off-label recommendations such as symptom-driven (as-needed) low dose ICS-formoterol and "low dose ICS taken whenever SABA is taken".The GINA 2019 report highlights significant updates in mild asthma management and these recommendations represent a clear deviation from decades of clinical practice mandating the use of symptom-driven SABA treatment alone in those with mild asthma. While the new inclusions of strategies such as symptom-driven (as-needed) ICS-formoterol and "ICS taken whenever SABA is taken" are based on several key trials, data in this context are still only emergent data, with clear superiority of as needed ICS-formoterol combinations over maintenance ICS regimens yet to be established for valid endpoints. Nevertheless, current and emerging data position the clinical asthma realm at a watershed moment with imminent changes for the way we manage mild asthma likely in going forward.
Fulltext Use of antibiotics and asthma medication for acute lower respiratory tract infections in people with and without asthma: retrospective cohort study

Denholm R, van der Werf ET, Hay AD

Respir Res, 2020 Jan 06;21(1):4.
PMID: 31906966 DOI: 10.1186/s12931-019-1233-5

BACKGROUND: Antibiotics are overused in patients with acute lower respiratory tract infections (ALRTIs), but less is known about their use in patients with asthma, or the use of asthma medication for ALRTI in patients without asthma. Our aim was to describe the frequency, variation and drivers in antibiotic and asthma medication prescribing for ALRTI in adults with and without asthma in primary care.
METHODS: A retrospective cohort analysis of patients aged ≥12 years, diagnosed with an ALRTI in primary care in 2014-15 was conducted using data from the Clinical Practice Research Datalink. Current asthma status, asthma medication and oral antibiotic use within 3 days of ALRTI infection was determined. Treatment frequency was calculated by asthma status. Mixed-effect regression models were used to explore between-practice variation and treatment determinants.
RESULTS: There were 127,976 ALRTIs reported among 110,418 patients during the study period, of whom 17,952 (16%) had asthma. Respectively, 81 and 79% of patients with and without asthma received antibiotics, and 41 and 15% asthma medication. There were significant differences in between-practice prescribing for all treatments, with greatest differences seen for oral steroids (odds ratio (OR) 18; 95% CI 7-82 and OR = 94; 33-363, with and without asthma) and asthma medication only (OR 7; 4-18 and OR = 17; 10-33, with and without asthma). Independent predictors of antibiotic prescribing among patients with asthma included fewer previous ALRTI presentations (≥2 vs. 0 previous ALRTI: OR = 0.25; 0.16-0.39), higher practice (OR = 1.47; 1.35-1.60 per SD) and prior antibiotic prescribing (3+ vs. 1 prescriptions OR = 1.28; 1.04-1.57) and concurrent asthma medication (OR = 1.44; 1.32-1.57). Independent predictors of asthma medication in patients without asthma included higher prior asthma medication prescribing (≥7 vs. 0 prescriptions OR = 2.31; 1.83-2.91) and concurrent antibiotic prescribing (OR = 3.59; 3.22-4.01).
CONCLUSION: Findings from the study indicate that antibiotics are over-used for ALRTI, irrespective of asthma status, and asthma medication is over-used in patients without asthma, with between-practice variation suggesting considerable clinical uncertainty. Further research is urgently needed to clarify the role of these medications for ALRTI.
Fulltext The association of spirometric small airways obstruction with respiratory symptoms, cardiometabolic diseases, and quality of life: results from the Burden of Obstructive Lung Disease (BOLD) study

Knox-Brown B, Patel J, Potts J, Ahmed R, Aquart-Stewart A, Barbara C, et al.

Respir Res, 2023 May 23;24(1):137.
PMID: 37221593 DOI: 10.1186/s12931-023-02450-1

BACKGROUND: Spirometric small airways obstruction (SAO) is common in the general population. Whether spirometric SAO is associated with respiratory symptoms, cardiometabolic diseases, and quality of life (QoL) is unknown.
METHODS: Using data from the Burden of Obstructive Lung Disease study (N = 21,594), we defined spirometric SAO as the mean forced expiratory flow rate between 25 and 75% of the FVC (FEF25-75) less than the lower limit of normal (LLN) or the forced expiratory volume in 3 s to FVC ratio (FEV3/FVC) less than the LLN. We analysed data on respiratory symptoms, cardiometabolic diseases, and QoL collected using standardised questionnaires. We assessed the associations with spirometric SAO using multivariable regression models, and pooled site estimates using random effects meta-analysis. We conducted identical analyses for isolated spirometric SAO (i.e. with FEV1/FVC ≥ LLN).
RESULTS: Almost a fifth of the participants had spirometric SAO (19% for FEF25-75; 17% for FEV3/FVC). Using FEF25-75, spirometric SAO was associated with dyspnoea (OR = 2.16, 95% CI 1.77-2.70), chronic cough (OR = 2.56, 95% CI 2.08-3.15), chronic phlegm (OR = 2.29, 95% CI 1.77-4.05), wheeze (OR = 2.87, 95% CI 2.50-3.40) and cardiovascular disease (OR = 1.30, 95% CI 1.11-1.52), but not hypertension or diabetes. Spirometric SAO was associated with worse physical and mental QoL. These associations were similar for FEV3/FVC. Isolated spirometric SAO (10% for FEF25-75; 6% for FEV3/FVC), was also associated with respiratory symptoms and cardiovascular disease.
CONCLUSION: Spirometric SAO is associated with respiratory symptoms, cardiovascular disease, and QoL. Consideration should be given to the measurement of FEF25-75 and FEV3/FVC, in addition to traditional spirometry parameters.