ABSTRACT
Key findings of this national survey of non-cystic fibrosis bronchiectasis epidemiology were that its prevalence, incidence and mortality have all increased over recent years; we estimate that around 212,000 people are currently living with bronchiectasis in the UK, very much higher than commonly quoted figures. Bronchiectasis is more common in females than males; 60% of diagnoses are made in the over-70 age group. Regional differences in prevalence, incidence, mortality, and hospital admission were identified. An intriguing finding was that bronchiectasis is more commonly diagnosed in the least deprived sections of the population, in contrast to other respiratory disorders.
Subject(s)
Bronchiectasis/epidemiology , Female , Humans , Male , National Health Programs/organization & administration , United Kingdom/epidemiologySubject(s)
Ethics, Professional , Pharmaceutical Services/history , Pharmacies/history , Societies, Pharmaceutical/history , History of Pharmacy , History, 17th Century , History, 18th Century , History, 19th Century , History, 20th Century , History, 21st Century , Humans , Pharmaceutical Services/ethics , Pharmacies/ethicsABSTRACT
BACKGROUND: Dr. Nelson's Improved Inhaler was first marketed with an advertisement in The Lancet in 1865. Revolutionary at the time for its ease of use and patient-friendliness, the inhaler is still in use for self-treatment by many all over the world. On the occasion of its 150th anniversary, this study reports an experimental historical medicine approach to identify evidence for the quality of vapor inhalers. METHODS: Through accessing reviews of the device's use by the contemporary medical establishment, it was established that Dr. Nelson's Inhaler enjoyed a reputation of quality and efficacy among reputable physicians generating empirical evidence of clinical performance. There was a general absence of product performance tests during this period. Therefore, modern inhalation performance testing was applied to test the aerosol delivery performance for Friars' Balsam, and its key chemical constituent, benzoic acid (BA). RESULTS: A respirable dose of 59.9 ± 9.0 µg of BA was aerosolized in a 10 minutes period from a dose of 3.3 mL Friars' Balsam (equivalent to 35.1 ± 0.2 mg of BA) in 375 mL of steaming water using the glass twin stage impinger at a flow rate of 60 L·min-1. The respirable dose from a standardized aqueous BA inhalation formulation increased from 115.9 ± 10.6 to 200.2 ± 19.9 µg by increasing the simulated inhalation period from 5 to 10 minutes. When tested with a simulated inhalation maneuver (500 mL tidal volume, 13 minutes-1 respiration rate, 1:2 inspiratory:expiratory ratio) a respirable dose of 112.8 ± 40.3 µg was produced. CONCLUSIONS: This work has highlighted the potential for aerosol drug delivery using steam inhalers that are popular with patients. Physicians should therefore be aware of the potential for lung dosing with irritants when patients self-medicate using the Nelson Inhaler with vaporizing formulations such as Friars' Balsam.
Subject(s)
Benzoic Acid/administration & dosage , Drug Delivery Systems , Nebulizers and Vaporizers , Technology, Pharmaceutical/methods , Administration, Inhalation , Aerosols/history , Equipment Design/history , History, 19th Century , Humans , Nebulizers and Vaporizers/history , Time FactorsABSTRACT
Patient-centredness is an accepted term and is perceived by healthcare professionals to be morally and ethically desirable. We are motivated by the belief that this approach will improve the patient-professional experience of the decision-making process and improve health outcomes. We acknowledge that patients, either as participants or as co-investigators, have positive contributions to make to research. As the idiopathic pulmonary fibrosis (IPF) community enters a new era of clinical research activity we consider that there is greater capacity for patient involvement and partnership.Patient involvement in research can be optimised through collaborations in the research design, study conduct, and dissemination. There is increasing interest in using patient- reported outcomes (PROs), such as health-related quality of life, and symptoms measures to inform decision-making and ensure patient perspectives are taken into account. PROs are an essential component of specialist IPF services, to monitor and improve care delivery and to measure and benchmark performance. In clinical trials, PROs can additionally be used to define entry criteria, evaluate efficacy of an intervention, and evaluate adverse events. We suggest that there is a much wider scope for including patient-centred PROs in clinical research and for creative thought in developing patient co-investigator roles.Participation in research activity requires highly refined decision-making processes, particularly in a condition such as IPF, which has an often unpredictable trajectory. The IPF research landscape has changed and the design and conduct of clinical trials in IPF requires some radical rethinking. It is accepted that involving patients in the role of co-investigators will impact the research questions we ask and result in study designs that are patient-centred. IPF clinical trials have been hindered by the lack of availability of validated, disease-specific questionnaires. A conservative approach appears to have been taken to the inclusion of generic symptom or quality of life measures as PRO endpoints. Thus, the impact of new drugs on the quality of life of research participants demonstrates only minimal benefit. It is time to refocus on a patient-centred approach with regards to the co-investigator role, PRO development, and research participants.
Subject(s)
Idiopathic Pulmonary Fibrosis/therapy , Patient Participation/trends , Research Design/trends , Female , Humans , Male , Outcome Assessment, Health Care , Quality of Life , Surveys and QuestionnairesSubject(s)
Biomedical Research/methods , Pulmonary Medicine , Respiratory Tract Diseases , Humans , United KingdomABSTRACT
During 2012, a number of respiratory drug projects and individual agents were discontinued, for a variety of reasons, including toxicity, lack of efficacy, commercial re-evaluation and change in corporate focus. These included three antagonists of chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTh2), which had been evaluated in allergic respiratory disease and (in one case) chronic obstructive pulmonary disease (COPD), and other agents intended for the treatment of asthma, COPD, pulmonary hypertension and lung fibrosis. These have been reviewed against the background of a general reduction in respiratory research by the pharmaceutical industry.
Subject(s)
Drugs, Investigational/therapeutic use , Lung Diseases/drug therapy , Respiratory System Agents/therapeutic use , Animals , Drug Industry , Drugs, Investigational/pharmacology , Humans , Respiratory System Agents/pharmacology , Treatment OutcomeABSTRACT
OBJECTIVE: To evaluate the efficacy and tolerability of the selective CRTh2 (DP2) receptor antagonist AZD1981 compared with placebo in patients with moderate to severe COPD. METHODS: In this multicentre, randomised, double-blind, parallel-group, phase IIa study (ClinicalTrials.gov identifier: NCT00690482) patients with moderate to severe COPD received either AZD1981 1000 mg twice daily or matching placebo for 4 weeks. Inhaled terbutaline was used as-needed as reliever medication throughout. The co-primary endpoints were change from baseline to end of treatment in pre-bronchodilator forced expiratory volume in 1 s [FEV1] and the Clinical COPD Questionnaire (CCQ). Additional endpoints included other lung function measures, 6-min walk test (6-MWT), COPD symptom score, reliever medication use and tolerability. RESULTS: 118 patients were randomised to treatment (AZD1981 n = 61; placebo n = 57); 83% of patients were male and the mean age was 63 years (range 43-83). There were no significant differences in the mean difference in change from baseline to end of treatment between AZD1981 and placebo for the co-primary endpoints of pre-bronchodilator FEV1 (AZD1981-placebo: -0.015, 95% CI: -0.10 to 0.070; p = 0.72) and CCQ total score (difference: 0.042, 95% CI: -0.21 to 0.30; p = 0.75). Similarly, no differences were observed between treatments for the other outcomes of lung function, COPD symptom score, 6-MWT, BODE index, and use of reliever medication. AZD1981 was well tolerated. CONCLUSION: There was no beneficial clinical effect of AZD1981, at a dose of 1000 mg twice daily for 4 weeks, in patients with moderate to severe COPD. AZD1981 was well tolerated and no safety concerns were identified.
Subject(s)
Acetates/therapeutic use , Bronchodilator Agents/therapeutic use , Indoles/therapeutic use , Pulmonary Disease, Chronic Obstructive/drug therapy , Receptors, Immunologic/antagonists & inhibitors , Receptors, Prostaglandin/antagonists & inhibitors , Acetates/adverse effects , Adult , Aged , Aged, 80 and over , Bronchodilator Agents/adverse effects , Double-Blind Method , Female , Forced Expiratory Volume/drug effects , Humans , Indoles/adverse effects , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/metabolism , Pulmonary Disease, Chronic Obstructive/pathology , Receptors, Immunologic/metabolism , Receptors, Prostaglandin/metabolism , Severity of Illness Index , Treatment Outcome , Vital Capacity/drug effectsABSTRACT
UNLABELLED: Neutrophil elastase (NE) activity is increased in bronchiectasis and may play a role in this condition. We wished to determine the effect of AZD9668, a selective oral inhibitor of NE. Efficacy and safety of AZD9668 60 mg twice daily over 4 weeks were evaluated in a randomised, double-blind, placebo-controlled, parallel-group, Phase II, signal-searching study in patients with bronchiectasis. Outcome measures included: waking and post-waking sputum neutrophil counts; lung function tests; 24-h sputum weight; BronkoTest(®) diary card data; St George's Respiratory Questionnaire for COPD patients (SGRQ-C); sputum NE activity; inflammatory biomarker levels; desmosine levels; adverse events, safety haematology and biochemistry. AZD9668 levels in plasma and sputum were measured to confirm exposure. Thirty-eight patients were randomised: 16 to placebo and 22 to AZD9668. There was no change in sputum neutrophils with AZD9668. Forced expiratory volume in 1 s improved by 100 mL in the AZD9668 group compared with placebo (p = 0.006). Significant changes (defined a priori as p < 0.1) in favour of AZD9668 were also seen in slow vital capacity, plasma interleukin-8, and post-waking sputum interleukin-6 and Regulated on Activation, Normal T-cell Expressed and Secreted levels. Non-significant changes in favour of AZD9668 were seen in other lung function tests, sputum weight and the SGRQ-C. AZD9668 was well tolerated. In this small signal-searching study, 4 weeks' treatment with AZD9668 improved lung function in patients with bronchiectasis and there were trends for reductions in sputum inflammatory biomarkers. Larger studies of longer duration would be needed to confirm the potential benefits of this agent in bronchiectasis. REGISTRATION: NCT00769119.
Subject(s)
Bronchiectasis/drug therapy , Proteinase Inhibitory Proteins, Secretory/therapeutic use , Pyridones/therapeutic use , Sulfones/therapeutic use , Administration, Oral , Adult , Aged , Bronchiectasis/metabolism , Bronchiectasis/physiopathology , Double-Blind Method , Drug Administration Schedule , Female , Humans , Inflammation Mediators/metabolism , Leukocyte Count , Leukocyte Elastase/metabolism , Male , Middle Aged , Neutrophils/pathology , Proteinase Inhibitory Proteins, Secretory/administration & dosage , Proteinase Inhibitory Proteins, Secretory/adverse effects , Proteinase Inhibitory Proteins, Secretory/pharmacokinetics , Pyridones/administration & dosage , Pyridones/adverse effects , Pyridones/pharmacokinetics , Respiratory Mechanics/drug effects , Sputum/cytology , Sputum/metabolism , Sulfones/administration & dosage , Sulfones/adverse effects , Sulfones/pharmacokinetics , Treatment Outcome , Walking/physiologyABSTRACT
INTRODUCTION: Interleukin-1 beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha) are potentially important in Chronic Obstructive Pulmonary Disease (COPD), but little is known of the relationships between these cytokines and their antagonists in disease compared with healthy controls. It is unclear if concentrations relate to disease severity. The study aimed to investigate these relationships and to assess the potential activity of each cytokine in the context of their antagonists. METHODS: Plasma cytokines, soluble receptors, and cell counts were measured in patients with stable COPD and age-matched healthy controls (n = 15 for both) daily for 5 days; these mediators were also measured in corresponding sputum samples from the COPD patients. RESULTS: COPD patients had significantly reduced concentrations of the antagonists, IL-1sRII, and IL-1RA compared with controls. In COPD, IL-1beta exceeded its antagonists and correlated significantly with BMI and FEV1, while plasma IL-1RA correlated positively with BMI but negatively with sputum IL-1beta, neutrophil, and macrophage counts and smoking history. TNFalpha antagonists exceeded agonists in both groups and did not correlate with COPD severity. CONCLUSIONS: Endogenous IL-1beta antagonists appear reduced in COPD. Furthermore, IL-1beta correlated with clinical aspects of disease severity, suggesting that IL-1beta may play a critical role in COPD. Given the relevant concentrations and binding affinities, it is likely that TNFalpha has limited activity in stable COPD.
Subject(s)
Cytokines/blood , Interleukin-1beta/blood , Pulmonary Disease, Chronic Obstructive/blood , Pulmonary Disease, Chronic Obstructive/immunology , Tumor Necrosis Factor-alpha/blood , Aged , Aged, 80 and over , Female , Humans , Interleukin 1 Receptor Antagonist Protein/blood , Interleukin-1beta/agonists , Interleukin-1beta/antagonists & inhibitors , Male , Middle Aged , Sputum/immunology , Tumor Necrosis Factor-alpha/agonists , Tumor Necrosis Factor-alpha/antagonists & inhibitorsABSTRACT
Biomarkers with potential utility in the diagnosis and prognosis of asthma and chronic obstructive pulmonary disease (COPD), and in monitoring the natural history of these diseases and the effect of therapeutic interventions, are being widely researched. This review critically describes the methodologies used for obtaining and analysing appropriate biofluid, tissue and exhaled breath samples for biomarker analysis. Currently measurements of sputum eosinophils and exhaled nitric oxide in asthmatics are the best established markers for disease activity and response to anti-inflammatory therapy. Circulating C-reactive protein (CRP) levels have been shown to predict risk of hospitalisation and death from COPD. Biomarker measurements in exhaled breath condensate are the least well-validated techniques. Other assessments in both conditions have potential value in clinical use but require further research and validation.
Subject(s)
Asthma/diagnosis , Biomarkers/analysis , Pulmonary Disease, Chronic Obstructive/diagnosis , Asthma/metabolism , Biopsy , Breath Tests , Bronchoalveolar Lavage , Humans , Nitric Oxide/analysis , Pulmonary Disease, Chronic Obstructive/metabolism , Sputum/chemistryABSTRACT
Over the last decade a number of novel viral respiratory pathogens have appeared or been recognized. Most of these are zoonoses, which have the capacity to infect humans directly or via an intermediate host. All but metapneumovirus are known to have caused epidemics of severe disease and at least two (the severe acute respiratory syndrome-coronavirus and influenza H5N1) have the potential to cause global pandemics. Possible preventive measures and treatment options against these new diseases are discussed in this review.
Subject(s)
Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/microbiology , Animals , Clinical Trials as Topic , Hantavirus Pulmonary Syndrome/drug therapy , Hantavirus Pulmonary Syndrome/epidemiology , Hantavirus Pulmonary Syndrome/microbiology , Hendra Virus , Humans , Influenza, Human , Metapneumovirus , Paramyxoviridae Infections/drug therapy , Paramyxoviridae Infections/epidemiology , Paramyxoviridae Infections/microbiology , Respiratory Tract Infections/epidemiology , Severe Acute Respiratory SyndromeSubject(s)
Antitubercular Agents/therapeutic use , Mycobacterium tuberculosis/drug effects , Tuberculosis, Pulmonary/drug therapy , Animals , Antitubercular Agents/pharmacology , Clinical Trials as Topic , Disease Susceptibility , Drug Design , Humans , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/immunology , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Pulmonary/genetics , Tuberculosis, Pulmonary/immunologyABSTRACT
In the past 30 years, more than 30 new aetiological agents of infectious disease have been identified. Some of these are responsible for entirely novel and life-threatening disorders, such as AIDS, Ebola fever, hantavirus pulmonary syndrome and Nipah virus encephalitis. During the same period, some longstanding infectious diseases (such as tuberculosis) have became resurgent, as a result of a combination of complacency, increased travel and social dislocation, and also increasing drug resistance. This review looks at some of the key unmet needs in this therapeutic area and discusses strategies to address them.
Subject(s)
Anti-Infective Agents/therapeutic use , Antiviral Agents/therapeutic use , Communicable Disease Control , Communicable Diseases/drug therapy , Viruses/pathogenicity , Communicable Diseases/epidemiology , Humans , Viruses/isolation & purificationABSTRACT
Anthrax being sent through the postal service brought the risks of bioterrorism home to us all: but what dies it really mean?