Therapeutic Advances in Respiratory Disease

Background: In the first 6 months following lung transplantation, the most frequently occurring complications are infection, acute rejection and anastomotic dysfunction. The utility of vibration response imaging (VRI) lung images in assisting with the detection of these complications was evaluated.

Objectives: The study aimed to evaluate if VRI is a good, non-invasive method of detecting clinical problems in lung transplant (LTx) recipients during early follow-up.

Methods: Between 06/2006 and 03/2007 all LTx patients who received transplants during the preceding 6 months at the Hannover Medical School received baseline VRI at enrolment with subsequent reassessment in combination with standard follow-up at 1, 3 and 6 months thereafter. The resulting images were analysed by two blinded reviewers.

Results: Fifty-five lung transplant recipients were enrolled in the study, with 49 patients successfully completing follow-up. Device operability and patient participation occurred without significant problems. High numbers of abnormal scans were detected. According to the clinical diagnosis, 29 patients (59.2 %) were stable at all four visits. Twenty clinical problems occurred (e.g., infections, rejections, obstructions, unknown deterioration). Agreement with clinical interpretation of rejections and infections was poor. Central airway obstruction (CAO) was detected in 80% by both reviewers. Accuracy in detecting obstructions was 89%; positive predicted value and negative predicted value were 80% and 90%, respectively.

Conclusion: The VRI system is a non-invasive easy-to-use method with technical success and good image quality. The high number of abnormal scans makes interpretation following LTx difficult. VRI was unable to detect deterioration in graft function with the exception of ventilation disorders like central airway complications.

Background: The ß2-adrenergic receptors are cell surface receptors playing a central role in the pharmacological targeting asthma and chronic obstructive pulmonary disease (COPD). Recent studies suggest that patients who are homozygous for one of the two important polymorphisms of the ß2-adrenergic receptor (ADRB2) gene at codon 16 (arginine to glycine) and 27 (glutamine to glutamate) may have a reduced response to ß2-agonists. Since smoking patients who are Gly16 homozygotes have an increased risk of airway obstruction we hypothesized that ß2-adrenoreceptor gene polymorphisms may be also a cofounder for COPD development and disease severity.

Methods: We investigated 190 COPD patients and 172 healthy volunteers in a case-control study. DNA was isolated from whole blood and ß2-AR gene polymorphisms Arg/Gly16 and Gln/Glu27 were determined using allele-specific polymerase chain reaction (PCR).

Results: In COPD patients with Gly/Gly16 was found more frequently than in healthy smokers (29.47% COPD versus 18.18% controls, p = 0.026). All other gene polymorphisms of the ADRB2 gene at codon 16 were equally distributed between groups. ß2-adrenoreceptor gene polymorphisms were neither a cofounder for COPD exacerbations (≥ 3 hospitalizations within the last 3 years) nor for disease severity (FEV1 ≤ 30% predicted).

Conclusion: Our study suggests that the Gly16 allele of the ß2-AR gene predisposes to COPD development but not for exacerbation rates and disease severity. In contrast, Gln/Glu27 polymorphism was irrelevant in our COPD cohort.

Asthma is estimated to affect approximately 4—11% of the general population and its prevalence is increasing continuously. A large number of epidemiological studies on the prevalence of asthma and the level of disease control have been carried out, in which the level of control defined by GINA objectives was shown to be significantly unsatisfactory. Frequently, patients accept suboptimal levels of asthma control, mainly because they do not know how asthma is caused and how it can be treated. Apart from having a deep negative impact on patient's daily life, undiagnosed and undercontrolled asthma can also mean an increased economic burden. Therefore, greater attention should be paid to preventive measures, patient education and self-management programmes. Scientific evidence exists that drugs currently available can achieve all or almost all the objectives indicated by international guidelines in the majority of patients, and to improve patients' HRQL by minimizing the impact of the disease and its treatment from the patient's viewpoint. In conclusion, there is a gap between the level of control that could be reached and what is obtained in real life. This must be reduced through a series of interventions in which both doctor and patient are involved.

Background: Exacerbations are common in chronic obstructive pulmonary disease (COPD) and contribute significantly to COPD morbidity and mortality. COPD is also associated with high levels of psychological distress, which has been shown to be associated with higher exacerbation rates. However, the existing literature on the association between psychological distress and exacerbation risk remains largely misunderstood.

Objectives: To critically review the current literature on the association between psychological distress (defined as anxiety and depressive symptoms or anxiety and depressive disorders) and COPD exacerbations in COPD patients, to highlight the limitations of the existing literature, and to provide recommendations for future research.

Methods: A critical review of English-language peer-reviewed longitudinal and retrospective studies was conducted. The Ovid portal to Medline, EMBASE, and PsycINFO databases were accessed.

Results: Some acceptable evidence suggested that psychological distress confers greater risk for exacerbations, more specifically symptom-based exacerbations or those treated in the patient’s own environment. However, most studies showed an absence of a positive association, especially with exacerbations leading to hospitalization.

Conclusions: Methodological weaknesses and the use of a wide range of psychological tools mean that there is an inconsistent association between psychological distress and exacerbations in the current literature. However, psychological distress may confer greater risk for symptom-based rather than event-based defined exacerbations. Further studies are needed to more comprehensively assess the question, particularly in light of the high levels of both anxiety and depression in COPD patients.

Analysis of exhaled breath condensate (EBC) is a noninvasive method for studying the composition of airway lining fluid and has the potential for assessing lung inflammation. EBC is mainly formed by water vapor, but also contains aerosol particles in which several biomolecules including leukotrienes, 8-isoprostane, prostaglandins, hydrogen peroxide, nitric oxide-derived products, and hydrogen ions, have been detected in healthy subjects. Inflammatory mediators in EBC are detected in healthy subjects and some of them are elevated in patients with different lung diseases. Analysis of EBC is completely noninvasive, is particularly suitable for longitudinal studies, and is potentially useful for assessing the response to pharmacological therapy. Identification of selective profiles of biomarkers of lung diseases might also have a diagnostic value. However, EBC analysis currently has important limitations. The lack of standardized procedures for EBC analysis and validation of some analytical techniques makes it difficult comparison of results from different laboratories. Analysis of EBC is currently more useful for relative measures than for quantitative assessment of inflammatory mediators. Reference analytical techniques are required to provide definitive evidence for the presence of some inflammatory mediators in EBC and for their accurate quantitative assessment in this biological fluid. Several methodological issues need to be addressed before EBC analysis can be considered for clinical applications. However, further research in this area is warranted due to the relative lack of noninvasive methods for assessing lung inflammation.

Background: The aim of our study was to compare the effects of montelukast and mometasone furoate nasal spray on the postoperative course of patients with nasal polyposis.

Patients and methods: Fifty patients diagnosed with nasal polyposis between March 2006 and August 2007 were included in the study. All patients underwent bilateral endoscopic sphenoethmoidectomy and were randomized postoperatively into two groups. Group A (n = 25) received 10 mg montelukast per day and group B (n = 25) received 400 µg mometasone furoate nasal spray twice daily. All patients were followed up for 6 months. Sino-Nasal Outcome Test (SNOT)-22 scores, polyp grades, computerized tomography (CT) scores (Lund–Mackay), eosinophils in peripheral blood and polyp tissue were evaluated before and after surgery.

Results: There was a significant reduction in SNOT-22 scores in both groups throughout the study period. There was a significant difference in the recurrence rate between both groups with a marginal advantage of mometasone furoate nasal spray. Eosinophils in peripheral blood were found to be effective on the recurrence rate (p < 0.05).

Conclusions: In conclusion, both drugs seem to have a complementary action and further studies are needed to determine which patients should receive which treatment.

Asthma and allergic rhinitis are common health problems that cause major illness and disability worldwide. The prevalence of allergic rhinitis is estimated to range from 10% to 20% in the USA and Europe. Multiple factors contribute to the wide range of reported prevalence rates. These include type of prevalence rate reported (current or cumulative), study selection criteria, age of participants, differences in survey methods, varied geographic locations and socioeconomic status, any of which are significant enough to confound direct comparison between studies. There is no standard set of diagnostic criteria for allergic rhinitis. In most studies, the criteria for diagnosis are based on the subject’s reporting, solely by questionnaire and rarely confirmed by skin testing. In addition, most studies focus on hay fever, leaving perennial allergic rhinitis underestimated. Sinus imaging is generally not performed and, therefore, rhinosinusitis not differentiated. Some investigators report ‘current’ prevalence while others report ‘cumulative’ or ‘lifetime’ prevalence. Epidemiologic studies have consistently shown that asthma and rhinitis often coexist in the same patients. The prevalence of asthma is <2% in subjects without rhinitis while it varies from 10% to 40% in patients with rhinitis. Furthermore, the majority of patients with asthma experience rhinitis, which is a factor in the risk for asthma. Despite recognition that allergic rhinitis and asthma are global health problems, there are insufficient epidemiologic data and more data are needed with regard to their etiologic risk factors and natural history. This aim of this review is to enable the reader to discuss prevalence, risk factors and prognosis of allergic rhinitis and asthma.

Pulmonary arterial hypertension (PAH) is a rare but well-known cardiovascular condition potentially associated with human immunodeficiency virus (HIV) infection and is currently recognized to be one of the most ominous noninfectious HIV complications. Although there is no clear evidence supporting the use of any medication for the treatment of HIV-related PAH, many of the currently available agents have been shown to exert some clinical benefits HIV-PAH patients. To date, no data are available regarding the potential effects of sitaxsentan, a selective endothelin type-A receptor antagonist, in this peculiar patient population. We report the case of a successful switch to sitaxsentan in a HIV-infected patient with PAH initially receiving bosentan who developed a late treatment-related side-effect.

Alpha-1 antitrypsin deficiency (AAT) is a hereditary recessive autosomal disease caused by mutations in the AAT gene. This disease is characterized by abnormally low AAT concentrations in plasma, which, in its homozygote form, carries a high risk for the development of early pulmonary emphysema and liver damage. Since the end of the 1980s augmentation therapy with AAT from human plasma has been available for specific treatment of emphysema due to AAT deficiency. Intravenous augmentation therapy has been demonstrated to be safe and weekly infusions of AAT have resulted in plasma AAT concentrations above those considered protective for the lungs. However, life-long weekly infusions are not well accepted by patients, therefore pharmacokinetic studies have been performed to try to individualize the therapeutic regimen in order to obtain adequate trough serum AAT levels with prolonged intervals of administration. Therapeutic regimens administered every two weeks appear to be safe and result in adequate trough serum concentrations, but less-frequent administrations result in trough levels below the target. Alpha-1-antitrypsin deficiency is largely unrecognized and underdiagnosed. The foundation of national and international registries is a valid strategy to increase awareness about the disease and collect information about the natural history of this deficiency. Furthermore, the identification of a large number of patients will allow the development of new clinical trials aimed at finding better treatments for this infrequent condition.

Objective: We performed a prospective study to investigate the the efficacy of seawater gel in reducing symptoms in patients with mild allergic rhinitis. We also aimed to investigate the impact of nasal irrigation on mucociliary clearance with seawater gel compared with saline in this patient group.

Methods: The study was performed in 100 consecutive adult individuals with a history of allergic rhinitis that was not controlled by anti-allergic drugs. Patients were assigned to receive seawater gel nasal spray for 10 days. The efficacy of treatment was assessed by means of total nasal symptom score and clinical findings.

Results: A statistically significant difference was found between scores of ‘nasal discharge, nasal obstruction, sneezing, nasal itching’before and after treatment (p < 0.001). Clinical findings evaluation revealed a statistically significant decrease in lower turbinate colour rating and turbinate congestion at the end of treatment (p< 0.001). Saccharin transit time decreased from baseline in the seawater trials by 12% compared with a 4% decrease for saline. The difference between the percent changes was statistically significant (t = 2.177; p < 0.05).

Conclusions: The present study provides evidence that a four times daily regimen of seawater gel can be an adjunctive therapy in the patient with allergic rhinitis.