The Challenge of Delivering Therapeutic Aerosols to Asthma Patients

ISRN Allergy
Volume 2013 (2013), Article ID 102418, 17 pages
http://dx.doi.org/10.1155/2013/102418

Review Article

The Challenge of Delivering Therapeutic Aerosols to Asthma Patients

Federico Lavorini

Department of Experimental and Clinical Medicine, Careggi University Hospital, Largo Brambilla 3, 50134, Florence, Italy

Received 16 May 2013; Accepted 23 June 2013

Academic Editors: G. Nicolini and F. Ram

Copyright © 2013 Federico Lavorini. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The number of people with asthma continues to grow around the world, and asthma remains a poorly controlled disease despite the availability of management guidelines and highly effective medication. Patient noncompliance with therapy is a major reason for poor asthma control. Patients fail to comply with their asthma regimen for a wide variety of reasons, but incorrect use of inhaler devices is amongst the most common. The pressurised metered-dose inhaler (pMDI) is still the most frequently used device worldwide, but many patients fail to use it correctly, even after repeated tuition. Breath-actuated inhalers are easier to use than pMDIs. The rationale behind inhaler choice should be evidence based rather than empirical. When choosing an inhaler device, it is essential that it is easy to use correctly, dosing is consistent, adequate drug is deposited in both central and peripheral airways, and that drug deposition is independent of airflow. Regular checking of inhalation technique is crucial, as correct inhalation is one of the cornerstones of successful asthma management.

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Research article

Facilitating education in pulmonary rehabilitation using the living well with COPD programme for pulmonary rehabilitation: a process evaluation

Denise Cosgrove, Joseph MacMahon, Jean Bourbeau, Judy M Bradley and Brenda O¿Neill

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BMC Pulmonary Medicine 2013, 13:50 doi:10.1186/1471-2466-13-50

Published: 5 August 2013

Abstract (provisional)

Background

Standardised evidenced-based materials and mechanisms to facilitate the delivery of the education component of pulmonary rehabilitation are not widely available. The aims of this study were: 1) to adapt the self-management programme Living Well with COPD (LWWCOPD) programme, for embedding in pulmonary rehabilitation; and, 2) to conduct a process evaluation of the adapted programme.

Methods

The adaptations to the LWWCOPD programme were informed by focus groups, current practice, relevant research and guideline documents. Pulmonary rehabilitation sites used the adapted programme, the LWWCOPD programme for pulmonary rehabilitation, to deliver the education component of pulmonary rehabilitation. A process evaluation was conducted: elements included reach (patients' attendance rates), dose delivered (amount of programme delivered), dose received (health professional and patient satisfaction) and fidelity (impact on patients' knowledge, understanding and self-efficacy on the Understanding COPD questionnaire). Descriptive statistics (mean, SD) were used to summarise demographics and key data from the feedback questionnaires. Qualitative feedback on the programme was collated and categorised. Changes in the Understanding COPD questionnaire were examined using paired t-tests.

Results

The LWWCOPD programme for pulmonary rehabilitation was delivered in eleven hospital- and community-based programmes (n=25 health professionals, n=57 patients with COPD). It consisted of six weekly 30--45 minute sessions. The process evaluation showed positive results: 62.3% of patients attended >= 4 education sessions (reach); mean (SD) 90 (10)% of the session content were delivered (dose delivered); the majority of sessions were rated as excellent or good by health professionals and patients. Patients' satisfaction was high: mean (SD) Section B of the Understanding COPD questionnaire: 91.67 (9.55)% (dose received). Knowledge, understanding and self-efficacy improved significantly: mean change (95% CI): Section A of the Understanding COPD questionnaire: 26.75 (21.74 to 31.76)%, BCKQ 10.64 (6.92 to 14.37)% (fidelity).

Conclusion

This rigorous process evaluation has demonstrated that the LWWCOPD programme for pulmonary rehabilitation can be used to deliver high quality, consistent and equitable education sessions during hospital and community-based pulmonary rehabilitation. This programme is now available worldwide (http://www.livingwellwithcopd.com/living-well-and-pulmonary-rehabilitation.html).

Trial registration: This study was registered with clinicaltrials.gov (reference number: NCT01226836).

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Research article

CTLA4-Ig (abatacept) therapy modulates T cell effector functions in autoantibody-positive rheumatoid arthritis patients.

Jennifer Pieper, Jessica Herrath, Sukanya Raghavan, Khalid Muhammad, Ronald van Vollenhoven and Vivianne Malmström

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BMC Immunology 2013, 14:34 doi:10.1186/1471-2172-14-34

Published: 5 August 2013

Abstract (provisional)

Background

Rheumatoid arthritis is a chronic inflammatory disease with a strong MHC class II component and where many patients develop characteristic autoantibodies towards the noncoding amino acid citrulline. Such anti-citrullinated protein antibodies (ACPA) have recently been put forward as an independent predictive factor for treatment response by co-stimulation blockade by CTLA4-Ig (abatacept). We have performed a mechanism of action study to dissect T cell functionality in RA patients with long-standing disease undergoing abatacept treatment and the influence of ACPA status.

Results

Peripheral blood samples were collected from RA patients as they started CTLA4-Ig treatment and 3 and 6 months later. A general decrease of regulatory T cell subsets was observed in the cohort. Additionally within the ACPA-positive group significant down-regulation of all key T cell effector subsets including Th1, Th2, and Th17 was observed by analyzing cytokines by intracellular flow cytometry and in cell culture supernatants.

RA synovial fluid samples were cultured in vitro in the presence or absence of CTLA4-Ig (abatacept). T cell cytokine production was diminished, but without increasing the functional capacity of CD4+CD25hi regulatory T cells as previously demonstrated in the context of TNF-blockade and anti-IL6R therapy.

Conclusions

Our immunological study of T cell functionality in RA patients, both ACPA-positive and ACPA-negative starting biological therapy with the co-stimulation blockade abatacept (CTLA4-Ig) supports the recently published registry study implicating ACPA seropositivity as an independent predictive factor to treatment response as we observed the most striking effect on T cell subset modulation in ACPA-positive patients. These data further support the notion of RA as a disease with several sub-entities, where the ACPA-positive fraction represents a classical HLA-associated autoimmune disorder while ACPA-negative patients may have other driving forces apart from classical adaptive immune responses.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

Letter to the Editor | Published 29 July 2013, doi:10.4414/smw.2013.13833
Cite this as: Swiss Med Wkly. 2013;143:w13833

High-altitude sojourn: a treatment option in allergic asthma

In a recently published paper, Dr L. Rijssenbeek et al. showed a strong beneficial effect of a high-altitude sojourn on both severe nonatopic and severe atopic asthma...

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Review article: Medical intelligence | Published 29 July 2013, doi:10.4414/smw.2013.13818
Cite this as: Swiss Med Wkly. 2013;143:w13818

Surfactant and allergic airway inflammation

Carla Winklera,b, Jens M. Hohlfelda,b,c

a Fraunhofer Institute for Experimental Medicine and Toxicology, Hannover, Germany
b Hannover Medical School, Germany
c Member of the German Centre for Lung Research, Hannover, Germany

Abstract

Pulmonary surfactant is a complex mixture of unique proteins and lipids that covers the airway lumen. Surfactant prevents alveolar collapse and maintains airway patency by reducing surface tension at the air-liquid interface. Furthermore, it provides a defence against antigen uptake by binding foreign particles and enhancing cellular immune responses. Allergic asthma is associated with chronic airway inflammation and presents with episodes of airway narrowing. The pulmonary inflammation and bronchoconstriction can be triggered by exposure to allergens or pathogens present in the inhaled air. Pulmonary surfactant has the potential to interact with various immune cells which orchestrate allergen- or pathogen-driven episodes of airway inflammation. The complex nature of surfactant allows multiple sites of interaction, but also makes it susceptible to external alterations, which potentially impair its function. This duality of modulating airway physiology and immunology during inflammatory conditions, while at the same time being prone to alterations accompanied by restricted function, has stimulated numerous studies in recent decades, which are reviewed in this article.

Key words: surfactant; allergic airway inflammation; surfactant therapy

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Journal of Asthma and Allergy

Effects of two inhaled corticosteroid/long-acting beta-agonist combinations on small-airway dysfunction in mild asthmatics measured by impulse oscillometry

Original Research

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Authors: Diong B, Singh K, Menendez R

Published Date August 2013 Volume 2013:6 Pages 109 - 116

DOI: http://dx.doi.org/10.2147/JAA.S48827

Received:	22 May 2013
Accepted:	02 July 2013
Published:	05 August 2013

Bill Diong,¹ Kshitiz Singh,² Rogelio Menendez^3
1School of Engineering, Southern Polytechnic State University, Marietta, GA, USA; ²College of Science and Engineering, Texas Christian University, Fort Worth, TX, USA; ³Allergy and Asthma Research Center of El Paso, El Paso, TX, USA

Background: We previously showed that the long-acting beta agonist (LABA) salmeterol as inhalation powder or metered-dose inhaler improves lung-function parameters assessed by impulse oscillometry (IOS) in 2- to 5-year-old children with reversible-airway disease within 15 minutes.
Objective: We studied 12- to 45-year-olds with mild persistent asthma in order to compare the onset and extent of peripheral airway effects following the first dose and after 4 weeks dosing with two inhaled corticosteroid (ICS)/LABA combinations: fluticasone propionate/salmeterol 115/21 and budesonide/formoterol 160/4.5.
Methods: Thirty subjects with mild persistent asthma using only an as-needed short-acting beta-agonist (albuterol) who had at least a 40% change in integrated low-frequency reactance postalbuterol were selected and randomized to receive either fluticasone propionate/salmeterol or budesonide/formoterol (15 subjects each). We collected three to six IOS replicates at baseline, at 5, 20, 40, 60, 120, and 240 minutes postdose at randomization, and after 4 weeks of twice-daily dosing. Blinded investigators calculated IOS frequency-dependent resistance and reactance (R5–R20 and AX), indicative of small-airway dysfunction, and also estimated the peripheral airway resistance (R_p) and peripheral airway compliance (C_p), using a respiratory-impedance model.
Results: At randomization visits, onset of action was detected as early as 5 minutes (t-test, P < 0.05) after fluticasone propionate/salmeterol by C_p, and within 5 minutes after budesonide/formoterol by R5–R20, AX, R_p, and C_p. However, after 4 weeks of dosing, only R_pwas significantly different (from 60 to 120 minutes) after fluticasone propionate/salmeterol, while R5–R20, AX, R_p, and C_p were not significantly different within 240 minutes after budesonide/formoterol.
Conclusion: These two ICS/LABA combinations initially improved the peripheral airway function of 12- to 45-year-old asthmatics significantly in about 5 minutes or less, as measured by R5–R20, AX, R_p, and/or C_p. After regular dosing for 4 weeks, pre- to postdose differences in these parameters had diminished significantly due to improved predose status of peripheral airways. Single dosing with ICS/LABA combinations in mild persistent asthma improves small-airway function, and the effect is maintained over a 12-hour interval by regular use for 4 weeks.

Keywords: asthma, ICS/LABA combination, impulse oscillometry parameters, lung-model parameters, peripheral airway resistance, peripheral airway compliance



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Front. Immunol., 05 August 2013 | doi: 10.3389/fimmu.2013.00229

Immune parameters to consider when choosing T-cell receptors for therapy

Scott R. Burrows^1,2 and John J. Miles^1,2,3*

• ¹Human Immunity Laboratory and Cellular Immunology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD, Australia
• ²School of Medicine, The University of Queensland, Brisbane, QLD, Australia
• ³Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, Wales, UK

T-cell receptor (TCR) therapy has arrived as a realistic treatment option for many human diseases. TCR gene therapy allows for the mass redirection of T-cells against a defined antigen while high affinity TCR engineering allows for the creation of a new class of soluble drugs. However, deciding which TCR blueprint to take forward for gene therapy or engineering is difficult. More than one quintillion TCR combinations can be generated by somatic recombination and we are only now beginning to appreciate that not all are functionally equal. TCRs can exhibit high or low degrees of HLA-restricted cross-reactivity and alloreact against one or a combination of HLA alleles. Identifying TCR candidates with high specificity and minimal cross-reactivity/alloreactivity footprints before engineering is obviously highly desirable. Here we will summarize what we currently know about TCR biology with regard to immunoengineering.

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Keywords: T-cell epitope, T-cell receptor, T-cell engineering

Citation: Burrows SR and Miles JJ (2013) Immune parameters to consider when choosing T-cell receptors for therapy. Front. Immunol. 4:229. doi: 10.3389/fimmu.2013.00229

Received: 11 May 2013; Accepted: 22 July 2013;
Published online: 05 August 2013.

Edited by:

Bruno Laugel, Cardiff University School of Medicine, UK

Reviewed by:

Liisa Kaarina Selin, University of Massachusetts Medical School, USA
Mirjam Heemskerk, Leiden University Medical Center, Netherlands

Copyright: © 2013 Burrows and Miles. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: John J. Miles, Human Immunity Laboratory, Queensland Institute of Medical Research, 300 Herston Road, Herston, Brisbane, QLD 4006, Australia e-mail: john.miles@qimr.edu.au

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