Current Respiratory Medicine Reviews - Volume 14, Issue 1, 2018

Background: Poor adherence to inhaled corticosteroid (ICS) therapy is a barrier to effective asthma management and a risk factor for morbidity and mortality. Attempts to improve adherence have had little measurable effect due to difficulty accurately measuring adherence and the complex nature of non-adherence. Electronic monitoring devices (EMDs) have been used in research to objectively monitor inhaler actuation; however, data on the effectiveness of EMDs in the clinical setting are sparse. Objective: This article reviews published, controlled studies employing EMDs as part of an intervention aimed at optimizing adherence in asthma and attempting to influence clinical outcomes. Method: Ovid Medline, Scopus and Web of Science were searched (July 2017) for studies using keywords related to asthma, inhaler technology, electronic monitoring and adherence. Data regarding study design, adherence and clinical outcomes were extracted. Results: Ten published studies representing 1469 randomised participants are included in this review. All but one study reported a significant difference in adherence between intervention and control groups; however, only two studies, both in children, were able to report sustained, significant improvements in clinical outcomes. One did so in asthma morbidity score and the other in asthma-related oral corticosteroid use and hospital admissions. Conclusion: Although EMDs show improvements in adherence, there is little current evidence to support that they reduce morbidity. Evidence of clinical effectiveness is needed to justify their common use in clinical practice and maximise their potential benefit. Carefully considered study design will be integral to demonstrating such clinical effectiveness.

Objectives: The post-sepsis syndrome characterized by the development of new psychiatric and cognitive deficits occurs in approximately 50% of sepsis survivors. This paper reviews the potential role of glucocorticoids, vitamin C and thiamine in limiting the development of the postsepsis syndrome. Data Sources and Study Selection: A PubMed literature review was performed for relevant articles. Only articles in English that studied sepsis were included. Data Extraction and Data Synthesis: Vitamin C is concentrated almost 100-fold in neurons and is the major antioxidant in the brain. Vitamin C deficiency is almost universal in patients with sepsis and increases cerebral oxidant injury, which has been linked to the development of delirium. Furthermore, vitamin C plays an essential role in the synthesis of neurotransmitters and in neuromodulation. Similarly, thiamine deficiency is common in sepsis and thiamine deficiency is well established to be associated with memory and cognitive dysfunction. Glucocorticoids play a central role in the adaptive response to stress, with exogenous glucocorticoid therapy having a proven role in reducing acute delirium and post-traumatic stress syndrome. Conclusion: We postulate that the treatment of severe sepsis with the combination of vitamin C, hydrocortisone and thiamine in addition to improving the short-term outcome of sepsis may reduce the development of the post-sepsis syndrome.

Allergic rhinitis (AR), more commonly known as hay fever, is a chronic type of rhinitis caused by exposure of a hypersensitive individual to a specific allergen. This response triggers the production of IgE antibodies, which in turn, binds to mast cells resulting in their degranulation, and subsequent release of inflammatory mediators (like histamine) within the bloodstream, leading to multiple nasal symptoms such as rhinorrhea, sneezing, nasal congestion and itching. For many years, AR has been a widely neglected and mistreated disorder where treatment is primarily based on the relief of symptoms, mostly treated with accessible over the counter drugs, so normally patients will tend to rely on self-medication before seeking proper medical attention. This understatement may be due to the fact that the disease is not ascribed to mortality. Nevertheless, this disease can have a significant impact on the quality of life of the patient. AR can be considered the second greatest cause of impairment of work productivity in the life of an afflicted individual. It is even worse than the impairment caused by other major diseases such as hypertension and diabetes mellitus. This review aims to present an overview of available important pharmacologic treatment options as well as alternative interventions, such as acupuncture/moxibustion, for the treatment of AR and its symptoms.

Background: The methyl-xanthine drug theophylline has been used for the treatment of asthma and chronic obstructive pulmonary disease (COPD) for several decades. Phosphodiesterase inhibition leading to smooth muscle relaxation is its main mode of action as a broncho-dilating agent, requiring blood theophylline concentrations close to the toxic range and a consequent problem with side effects. It also has anti-inflammatory effects that occur at relatively low concentrations. Objective: To explore supporting evidence for how other properties of theophylline could be of considerable clinical utility, particularly in reducing weakness and overt sarcopenia, based on its antiinflammatory, steroid-sparing and immune-modulating properties. Methods: PUBMED and MEDLINE were scanned using the search terms: theophylline, antiinflammatory, cytokine, inflammation, ageing, sarcopenia, frailty, chronic obstructive airways disease, pulmonary rehabilitation. High quality articles were selected, read in-depth and discussed by the authors, then used as the basis for a proposition on the potential anti-inflammatory and antisarcopenic use of theophylline. Findings: The anti-inflammatory properties of theophylline are mainly mediated by histone deacetylase induction in immune competent cells with a resulting shift toward the expression of a less inflamed phenotype, including a reduction of the release of pro-inflammatory cytokines and the associated increase in anti-inflammatory cytokines. These effects occur at blood theophylline concentrations well below the range for direct broncho-dilatation. Conclusion: There are potential therapeutic benefits of theophylline that are systemic and not confined to airways inflammation in COPD. There is scope for a beneficial effect in other chronic inflammatory states and post-acute inflammation with slow resolution. There is compelling evidence that theophylline could be used for anti-inflammatory adjunctive treatment to improve independent function, muscle strength and other outcomes in individuals recovering from acute inflammatory episodes, including but not limited to exacerbations of COPD, and as a pharmaceutical intervention in support of pulmonary rehabilitation.

Procalcitonin was introduced to management of hospital-acquired pneumonia/ventilatorassociated pneumonia (HAP/VAP) by the American Thoracic Society/Infectious Disease Society of America (ATS/IDSA), in its 2005 HAP guidelines. It was based on the assumption that positive procalcitonin (PCT) results indicative of HAP/VAP of bacterial aetiology will prompt antibiotic therapy, and improve clinical outcomes. Antibiotic stewardship by monitoring of PCT kinetics resulted in shorter antibiotic treatment durations with early cessation of therapies. The diagnostic part is no more recommended due to weak evidence from studies. Beyond diagnostic uses, some studies have shown that positive PCT levels are associated with poorer clinical outcomes in HAP/VAP, Healthcare-associated pneumonia and community-acquired pneumonia. The article will discuss the diagnostic role briefly and mainly the role as a prognostic indicator in the management of HAP/VAP.

Background: The accurate microscopic diagnosis of lung cancer has become insufficient due to the concept of personalized medicine. Tissue samples are used not only for microscopic diagnosis but also for the assessment of the different targets. Biopsies are performed in 80% of the patients and they are not sufficient for molecular diagnosis in 30 % of the cases. Liquid biopsy (LB) has been reported as a possible surrogate to tissue samples and has been introduced in the management scheme of the patients since 2014. We aimed to highlight the diagnostic value of liquid biopsy in assessing the molecular profile of non small cell carcinomas in comparison with tissue biopsy. Methods: We retracted eligible articles from PubMed, Embase and Cochrane databases. We calculated the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR). A summary receiver operating characteristic curve (SROC) and area under curve (AUC) were used to evaluate the overall diagnostic performance using the Meta-Disc software 5.1.32. The heterogeneity was assessed using I square statistics. A metaregression was performed in case of heterogeneity. In case of absence of covariates, a sensitivity analysis was done in order to assess publications that induced a statistical bias. Results: 39 eligible studies involving 4782 patients were included. The overall statistical studies showed heterogeneity in the SEN, SPE, PLR, NLR and DOR. No threshold effect was revealed. The meta-regression incorporating the ethnicity, the test, the technique used in tissue and plasma and the use of plasma or serum as covariates showed no impact of these factors. A sensitivity analysis allowed achieving the homogeneity in the SPE and DOR. The overall pooled SEN and SPE were 0.61 and 0.95 respectively. The PLR was 9.51, the NLR was 0.45 and DOR was 24.58. The SROC curve with AUC of 0,93 indicated that the liquid biopsy is capable of identifying wild type samples from mutated ones with a relatively high accuracy. Conclusion: This meta-analysis suggested that detection of molecular mutations by cfDNA is of adequate diagnostic accuracy in association to tissues. The high specificity and the moderate sensitivity highlight the value of LB as a screening test.