Out & Online effectiveness of a tailored online multi-symptom mental health and wellbeing program for same-sex attracted young adults: Study protocol for a randomised controlled trial
- Abbott, Jo-Anne, Klein, Britt, McLaren, Suzanne, Austin, David, Molloy, Mari, Meyer, Denny, McLeod, Bronte
- Authors: Abbott, Jo-Anne , Klein, Britt , McLaren, Suzanne , Austin, David , Molloy, Mari , Meyer, Denny , McLeod, Bronte
- Date: 2014
- Type: Text , Journal article
- Relation: Trials Vol. 15, no. 1 (2014), p. 1-19
- Full Text:
- Reviewed:
- Description: Background: Same-sex attracted young adults have been found to experience higher rates of mental health problems and greater difficulties in accessing specialist mental health care services compared to their heterosexual peers. Internet-based mental health interventions have the potential to be more engaging and accessible to young adults compared to those delivered face-to-face. However, they are rarely inclusive of lesbian women and gay men. Thus, the current study aims to evaluate the effectiveness of an online mental health and wellbeing program, Out & Online (http://www.outandonline.org.au), in comparison to a wait-list control group, for reducing anxiety and depressive symptoms in same-sex attracted young adults aged between 18 and 25 years. Methods/Design: We are recruiting, through media and community organisations, 200 same-sex attracted young adults with anxiety and/or depressive symptoms and mild to moderate psychological distress (Kessler-10 score between 16 to 21). Participants will be randomly allocated to the intervention (the online program) or the wait-list control group based on a permuted blocked randomisation method to allow for stratification by gender. Participants in the intervention group will receive a tailored program for up to three types of mental health difficulties simultaneously. The primary outcome of anxiety and/or depressive symptoms, and secondary outcomes related to psychological distress, wellbeing and health behaviour will be measured at pre-intervention (0 week), post-intervention (8 weeks) and at a 3-month follow-up (20 weeks). Discussion: This online mental health and wellbeing program will be one of the first online interventions to be designed specifically to be relevant for same-sex attracted individuals. If the program is found to be effective it will improve access to specialist same-sex attracted-relevant mental health services for young adults and will facilitate wellbeing outcomes for these individuals. This program will also be a significant development in the delivery of tailored interventions that target multiple types of mental health conditions simultaneously. © 2014 Abbott et al.
- Authors: Abbott, Jo-Anne , Klein, Britt , McLaren, Suzanne , Austin, David , Molloy, Mari , Meyer, Denny , McLeod, Bronte
- Date: 2014
- Type: Text , Journal article
- Relation: Trials Vol. 15, no. 1 (2014), p. 1-19
- Full Text:
- Reviewed:
- Description: Background: Same-sex attracted young adults have been found to experience higher rates of mental health problems and greater difficulties in accessing specialist mental health care services compared to their heterosexual peers. Internet-based mental health interventions have the potential to be more engaging and accessible to young adults compared to those delivered face-to-face. However, they are rarely inclusive of lesbian women and gay men. Thus, the current study aims to evaluate the effectiveness of an online mental health and wellbeing program, Out & Online (http://www.outandonline.org.au), in comparison to a wait-list control group, for reducing anxiety and depressive symptoms in same-sex attracted young adults aged between 18 and 25 years. Methods/Design: We are recruiting, through media and community organisations, 200 same-sex attracted young adults with anxiety and/or depressive symptoms and mild to moderate psychological distress (Kessler-10 score between 16 to 21). Participants will be randomly allocated to the intervention (the online program) or the wait-list control group based on a permuted blocked randomisation method to allow for stratification by gender. Participants in the intervention group will receive a tailored program for up to three types of mental health difficulties simultaneously. The primary outcome of anxiety and/or depressive symptoms, and secondary outcomes related to psychological distress, wellbeing and health behaviour will be measured at pre-intervention (0 week), post-intervention (8 weeks) and at a 3-month follow-up (20 weeks). Discussion: This online mental health and wellbeing program will be one of the first online interventions to be designed specifically to be relevant for same-sex attracted individuals. If the program is found to be effective it will improve access to specialist same-sex attracted-relevant mental health services for young adults and will facilitate wellbeing outcomes for these individuals. This program will also be a significant development in the delivery of tailored interventions that target multiple types of mental health conditions simultaneously. © 2014 Abbott et al.
A phase II trial for the efficacy of physiotherapy intervention for early-onset hip osteoarthritis: Study protocol for a randomised controlled trial
- Kemp, Joanne, Moore, Kate, Fransen, Marlene, Russell, Trevor, Crossley, Kay
- Authors: Kemp, Joanne , Moore, Kate , Fransen, Marlene , Russell, Trevor , Crossley, Kay
- Date: 2015
- Type: Text , Journal article
- Relation: Trials Vol. 16, no. 1 (2015), p. 1-8
- Full Text:
- Reviewed:
- Description: Background: Early-onset hip osteoarthritis is commonly seen in people undergoing hip arthroscopy and is associated with increased pain, reduced ability to participate in physical activity, reduced quality of life and reduced range of motion and muscle strength. Despite this, the efficacy of non-surgical interventions such as exercise therapies remains unknown. The primary aim is to establish the feasibility of a phase III randomised controlled trial investigating a targeted physiotherapy intervention for people with early-onset hip osteoarthritis. The secondary aims are to determine the size of treatment effects of a physiotherapy intervention, targeted to improve hip joint range and hip-related symptoms in early-onset hip osteoarthritis following hip arthroscopy, compared to a health-education control. Methods: This protocol describes a randomised, assessor- and participant-blind, controlled clinical trial. We will include 20 participants who are (i) aged between 18 and 50 years; (ii) have undergone hip arthroscopy during the past six to 12 months; (iii) have early-onset hip osteoarthritis (defined as chondrolabral pathology) at the time of hip arthroscopy; and (iv) experience hip-related pain during activities. Primary outcome will be the feasibility of a phase III clinical trial. Secondary outcomes will be (i) perceived global change score; (ii) hip-related symptoms (measured using the Hip disability and Osteoarthritis Outcome Score (HOOS) pain subscale, activity subscale, and sport and recreation subscale); (iii) hip quality of life (measured using the HOOS quality of life subscale and International Hip Outcome tool; (iv) hip muscle strength and (v) hip range of motion. The physiotherapy intervention is semi-standardised, including joint and soft tissue mobilisation and stretching, hip and trunk muscle retraining and functional and activity-specific retraining and education. The control intervention encompasses individualised health education, with the same frequency and duration as the intervention. The trial primary end-point is the conclusion of the 12-week intervention, and follow-up measures will be collected at the 12-week post-baseline assessment. Discussion: The findings of this study will provide guidance regarding the feasibility of a full-scale phase III randomised controlled trial, prior to its undertaking. Trial registration: The trial protocol was registered with the Australian Clinical Trials Registry (number: 12614000426684) on 17 April 2014. © Kemp et al.
- Authors: Kemp, Joanne , Moore, Kate , Fransen, Marlene , Russell, Trevor , Crossley, Kay
- Date: 2015
- Type: Text , Journal article
- Relation: Trials Vol. 16, no. 1 (2015), p. 1-8
- Full Text:
- Reviewed:
- Description: Background: Early-onset hip osteoarthritis is commonly seen in people undergoing hip arthroscopy and is associated with increased pain, reduced ability to participate in physical activity, reduced quality of life and reduced range of motion and muscle strength. Despite this, the efficacy of non-surgical interventions such as exercise therapies remains unknown. The primary aim is to establish the feasibility of a phase III randomised controlled trial investigating a targeted physiotherapy intervention for people with early-onset hip osteoarthritis. The secondary aims are to determine the size of treatment effects of a physiotherapy intervention, targeted to improve hip joint range and hip-related symptoms in early-onset hip osteoarthritis following hip arthroscopy, compared to a health-education control. Methods: This protocol describes a randomised, assessor- and participant-blind, controlled clinical trial. We will include 20 participants who are (i) aged between 18 and 50 years; (ii) have undergone hip arthroscopy during the past six to 12 months; (iii) have early-onset hip osteoarthritis (defined as chondrolabral pathology) at the time of hip arthroscopy; and (iv) experience hip-related pain during activities. Primary outcome will be the feasibility of a phase III clinical trial. Secondary outcomes will be (i) perceived global change score; (ii) hip-related symptoms (measured using the Hip disability and Osteoarthritis Outcome Score (HOOS) pain subscale, activity subscale, and sport and recreation subscale); (iii) hip quality of life (measured using the HOOS quality of life subscale and International Hip Outcome tool; (iv) hip muscle strength and (v) hip range of motion. The physiotherapy intervention is semi-standardised, including joint and soft tissue mobilisation and stretching, hip and trunk muscle retraining and functional and activity-specific retraining and education. The control intervention encompasses individualised health education, with the same frequency and duration as the intervention. The trial primary end-point is the conclusion of the 12-week intervention, and follow-up measures will be collected at the 12-week post-baseline assessment. Discussion: The findings of this study will provide guidance regarding the feasibility of a full-scale phase III randomised controlled trial, prior to its undertaking. Trial registration: The trial protocol was registered with the Australian Clinical Trials Registry (number: 12614000426684) on 17 April 2014. © Kemp et al.
Cognitive behaviour therapy for older adults experiencing insomnia and depression in a community mental health setting: Study protocol for a randomised controlled trial
- Sadler, Paul, McLaren, Suzanne, Klein, Britt, Jenkins, Megan, Harvey, Jack
- Authors: Sadler, Paul , McLaren, Suzanne , Klein, Britt , Jenkins, Megan , Harvey, Jack
- Date: 2015
- Type: Text , Journal article
- Relation: Trials Vol. 16, no. 1 (2015), p.1-12
- Full Text:
- Reviewed:
- Description: Background: Cognitive behaviour therapy for insomnia (CBT-I) is a well-established treatment; however, the evidence is largely limited to homogenous samples. Although emerging research has indicated that CBT-I is also effective for comorbid insomnia, CBT-I has not been tested among a complex sample of older adults with comorbid insomnia and depression. Furthermore, no study has explored whether modifying CBT-I to target associated depressive symptoms could potentially enhance sleep and mood outcomes. Therefore, this study aims to report a protocol designed to test whether an advanced form of CBT for insomnia and depression (CBT-I-D) is more effective at reducing insomnia and depressive symptoms compared to a standard CBT-I and psychoeducation control group (PCG) for older adults in a community mental health setting. Methods/Design: We aim to recruit 150 older adults with comorbid insomnia who have presented to community mental health services for depression. Eligible participants will be randomly allocated via block/cluster randomisation to one of three group therapy conditions: CBT-I, CBT-I-D, or PCG. Participants who receive CBT-I will only practice strategies designed to improve their sleep, whereas participants who receive CBT-I-D will practice additional strategies designed to also improve their mood. This trial will implement a mixed-methods design involving quantitative outcome measures and qualitative focus groups. The primary outcome measures are insomnia and depression severity, and secondary outcomes are anxiety, hopelessness, beliefs about sleep, comorbid sleep conditions, and health. Outcomes will be assessed at pre-intervention (week 0), post-intervention (week 8), and 3-month follow-up (week 20). Discussion: This CBT study protocol has been designed to address comorbid insomnia and depression for older adults receiving community mental health services. The proposed trial will determine whether CBT-I is more effective for older adults with comorbid insomnia and depression compared to a PCG. It will also establish whether an advanced form of CBT-I-D generates greater reductions in insomnia and depression severity compared to standard CBT-I. The results from the proposed trial are anticipated to have important clinical implications for older adults, researchers, therapists, and community mental health services. Trial registration: Australian and New Zealand Clinical Trials Registry (ANZCTR): ACTRN: 12615000067572 , Date Registered 12 December 2014. © 2015 Sadler et al.
- Authors: Sadler, Paul , McLaren, Suzanne , Klein, Britt , Jenkins, Megan , Harvey, Jack
- Date: 2015
- Type: Text , Journal article
- Relation: Trials Vol. 16, no. 1 (2015), p.1-12
- Full Text:
- Reviewed:
- Description: Background: Cognitive behaviour therapy for insomnia (CBT-I) is a well-established treatment; however, the evidence is largely limited to homogenous samples. Although emerging research has indicated that CBT-I is also effective for comorbid insomnia, CBT-I has not been tested among a complex sample of older adults with comorbid insomnia and depression. Furthermore, no study has explored whether modifying CBT-I to target associated depressive symptoms could potentially enhance sleep and mood outcomes. Therefore, this study aims to report a protocol designed to test whether an advanced form of CBT for insomnia and depression (CBT-I-D) is more effective at reducing insomnia and depressive symptoms compared to a standard CBT-I and psychoeducation control group (PCG) for older adults in a community mental health setting. Methods/Design: We aim to recruit 150 older adults with comorbid insomnia who have presented to community mental health services for depression. Eligible participants will be randomly allocated via block/cluster randomisation to one of three group therapy conditions: CBT-I, CBT-I-D, or PCG. Participants who receive CBT-I will only practice strategies designed to improve their sleep, whereas participants who receive CBT-I-D will practice additional strategies designed to also improve their mood. This trial will implement a mixed-methods design involving quantitative outcome measures and qualitative focus groups. The primary outcome measures are insomnia and depression severity, and secondary outcomes are anxiety, hopelessness, beliefs about sleep, comorbid sleep conditions, and health. Outcomes will be assessed at pre-intervention (week 0), post-intervention (week 8), and 3-month follow-up (week 20). Discussion: This CBT study protocol has been designed to address comorbid insomnia and depression for older adults receiving community mental health services. The proposed trial will determine whether CBT-I is more effective for older adults with comorbid insomnia and depression compared to a PCG. It will also establish whether an advanced form of CBT-I-D generates greater reductions in insomnia and depression severity compared to standard CBT-I. The results from the proposed trial are anticipated to have important clinical implications for older adults, researchers, therapists, and community mental health services. Trial registration: Australian and New Zealand Clinical Trials Registry (ANZCTR): ACTRN: 12615000067572 , Date Registered 12 December 2014. © 2015 Sadler et al.
Dynamics of IL-4 and IL-13 expression in the airways of sheep following allergen challenge
- Liravi, Bahar, Piedrafita, David, Nguyen, Gary, Bischof, Robert
- Authors: Liravi, Bahar , Piedrafita, David , Nguyen, Gary , Bischof, Robert
- Date: 2015
- Type: Text , Journal article
- Relation: BMC Pulmonary Medicine Vol. 15, no. 1 (2015), p. 1-11
- Full Text:
- Reviewed:
- Description:
Background: IL-4 and IL-13 play a critical yet poorly understood role in orchestrating the recruitment and activation of effector cells of the asthmatic response and driving the pathophysiology of allergic asthma. The house dust mite (HDM) sheep asthma model displays many features of the human condition and is an ideal model to further elucidate the involvement of these critical Th
2 cytokines. We hypothesized that airway exposure to HDM allergen would induce or elevate the expression profile of IL-4 and IL-13 during the allergic airway response in this large animal model of asthma. Methods: Bronchoalveolar lavage (BAL) samples were collected from saline-and house dust mite (HDM)-challenged lung lobes of sensitized sheep from 0 to 48h post-challenge. BAL cytokines (IL-4, IL-13, IL-6, IL-10, TNF-aα) were each measured by ELISA. IL-4 and IL-13 expression was assessed in BAL leukocytes by flow cytometry and in airway tissue sections by immunohistology. Results: IL-4 and IL-13 were increased in BAL samples following airway allergen challenge. HDM challenge resulted in a significant increase in BAL IL-4 levels at 4h compared to saline-challenged airways, while BAL IL-13 levels were elevated at all time-points after allergen challenge. IL-6 levels were maintained following HDM challenge but declined after saline challenge, while HDM administration resulted in an acute elevation in IL-10 at 4h but no change in TNF-aα levels over time. Lymphocytes were the main early source of IL-4, with IL-4 release by alveolar macrophages (AMs) prominent from 24h post-allergen challenge. IL-13 producing AMs were increased at 4 and 24h following HDM compared to saline challenge, and tissue staining provided evidence of IL-13 expression in airway epithelium as well as immune cells in airway tissue. Conclusion: In a sheep model of allergic asthma, airway inflammation is accompanied by the temporal release of key cytokines following allergen exposure that primarily reflects the Th2 -driven nature of the immune response in asthma. The present study demonstrates for the first time the involvement of IL-4 and IL-13 in a relevant large animal model of allergic airways disease. © 2015 Liravi et al.
- Authors: Liravi, Bahar , Piedrafita, David , Nguyen, Gary , Bischof, Robert
- Date: 2015
- Type: Text , Journal article
- Relation: BMC Pulmonary Medicine Vol. 15, no. 1 (2015), p. 1-11
- Full Text:
- Reviewed:
- Description:
Background: IL-4 and IL-13 play a critical yet poorly understood role in orchestrating the recruitment and activation of effector cells of the asthmatic response and driving the pathophysiology of allergic asthma. The house dust mite (HDM) sheep asthma model displays many features of the human condition and is an ideal model to further elucidate the involvement of these critical Th
2 cytokines. We hypothesized that airway exposure to HDM allergen would induce or elevate the expression profile of IL-4 and IL-13 during the allergic airway response in this large animal model of asthma. Methods: Bronchoalveolar lavage (BAL) samples were collected from saline-and house dust mite (HDM)-challenged lung lobes of sensitized sheep from 0 to 48h post-challenge. BAL cytokines (IL-4, IL-13, IL-6, IL-10, TNF-aα) were each measured by ELISA. IL-4 and IL-13 expression was assessed in BAL leukocytes by flow cytometry and in airway tissue sections by immunohistology. Results: IL-4 and IL-13 were increased in BAL samples following airway allergen challenge. HDM challenge resulted in a significant increase in BAL IL-4 levels at 4h compared to saline-challenged airways, while BAL IL-13 levels were elevated at all time-points after allergen challenge. IL-6 levels were maintained following HDM challenge but declined after saline challenge, while HDM administration resulted in an acute elevation in IL-10 at 4h but no change in TNF-aα levels over time. Lymphocytes were the main early source of IL-4, with IL-4 release by alveolar macrophages (AMs) prominent from 24h post-allergen challenge. IL-13 producing AMs were increased at 4 and 24h following HDM compared to saline challenge, and tissue staining provided evidence of IL-13 expression in airway epithelium as well as immune cells in airway tissue. Conclusion: In a sheep model of allergic asthma, airway inflammation is accompanied by the temporal release of key cytokines following allergen exposure that primarily reflects the Th2 -driven nature of the immune response in asthma. The present study demonstrates for the first time the involvement of IL-4 and IL-13 in a relevant large animal model of allergic airways disease. © 2015 Liravi et al.
Bronchial thermoplasty reduces airway resistance
- Langton, David, Bennetts, Kim, Noble, Peter, Plummer, Virginia, Thien, Francis
- Authors: Langton, David , Bennetts, Kim , Noble, Peter , Plummer, Virginia , Thien, Francis
- Date: 2020
- Type: Text , Journal article
- Relation: Respiratory Research Vol. 21, no. 1 (2020), p.
- Full Text:
- Reviewed:
- Description: Background: The mechanism for symptomatic improvement after bronchial thermoplasty (BT) is unclear, since spirometry reveals little or no change. In this study, the effects of BT on airway resistance were examined using two independent techniques. Methods: Eighteen consecutive patients, with severe asthma (57.6 ± 14.2 years) were evaluated by spirometry and plethysmography at three time points: (i) baseline, (ii) left lung treated but right lung untreated and (iii) 6 weeks after both lungs were treated with BT. At each assessment, total and specific airway resistance (Raw, sRaw) were measured. High resolution CT scans were undertaken at the first two assessments, and measurements of lobar volume, airway volume and airway resistance were made. The Asthma Control Questionnaire (ACQ) was administered at each assessment. Results: The baseline ACQ score was 3.5 ± 0.9, and improved progressively to 1.8 ± 1.2 (p < 0.01). At baseline, severe airflow obstruction was observed, FEV1 44.8 ± 13.7% predicted, together with gas trapping, and elevated Raw at 342 ± 173%predicted. Following BT, significant improvements in Raw and sRaw were observed, as well as a reduction in Residual Volume, increase in Vital Capacity and no change in FEV1. The change in Raw correlated with the change in ACQ (r = 0.56, p < 0.05). CT scans demonstrated reduced airway volume at baseline, which correlated with the increased Raw determined by plethysmography (p = - 0.536, p = < 0.05). Following BT, the airway volume increased in the treated lung, and this was accompanied by a significant reduction in CT-determined local airway resistance. Conclusion: Symptomatic improvement after BT is mediated by increased airway volume and reduced airway resistance. © 2020 The Author(s).
- Authors: Langton, David , Bennetts, Kim , Noble, Peter , Plummer, Virginia , Thien, Francis
- Date: 2020
- Type: Text , Journal article
- Relation: Respiratory Research Vol. 21, no. 1 (2020), p.
- Full Text:
- Reviewed:
- Description: Background: The mechanism for symptomatic improvement after bronchial thermoplasty (BT) is unclear, since spirometry reveals little or no change. In this study, the effects of BT on airway resistance were examined using two independent techniques. Methods: Eighteen consecutive patients, with severe asthma (57.6 ± 14.2 years) were evaluated by spirometry and plethysmography at three time points: (i) baseline, (ii) left lung treated but right lung untreated and (iii) 6 weeks after both lungs were treated with BT. At each assessment, total and specific airway resistance (Raw, sRaw) were measured. High resolution CT scans were undertaken at the first two assessments, and measurements of lobar volume, airway volume and airway resistance were made. The Asthma Control Questionnaire (ACQ) was administered at each assessment. Results: The baseline ACQ score was 3.5 ± 0.9, and improved progressively to 1.8 ± 1.2 (p < 0.01). At baseline, severe airflow obstruction was observed, FEV1 44.8 ± 13.7% predicted, together with gas trapping, and elevated Raw at 342 ± 173%predicted. Following BT, significant improvements in Raw and sRaw were observed, as well as a reduction in Residual Volume, increase in Vital Capacity and no change in FEV1. The change in Raw correlated with the change in ACQ (r = 0.56, p < 0.05). CT scans demonstrated reduced airway volume at baseline, which correlated with the increased Raw determined by plethysmography (p = - 0.536, p = < 0.05). Following BT, the airway volume increased in the treated lung, and this was accompanied by a significant reduction in CT-determined local airway resistance. Conclusion: Symptomatic improvement after BT is mediated by increased airway volume and reduced airway resistance. © 2020 The Author(s).
Effective pulmonary delivery of an aerosolized plasmid DNA vaccine via surface acoustic wave nebulization
- Rajapaksa, Anushi, Ho, Jenny, Qi, Aaisha, Bischof, Robert, Nguyen, Tri-Hung, Tate, Michelle, Piedrafita, David, McIntosh, Michelle, Yeo, Leslie, Meeusen, Els, Coppel, Ross, Friend, James
- Authors: Rajapaksa, Anushi , Ho, Jenny , Qi, Aaisha , Bischof, Robert , Nguyen, Tri-Hung , Tate, Michelle , Piedrafita, David , McIntosh, Michelle , Yeo, Leslie , Meeusen, Els , Coppel, Ross , Friend, James
- Date: 2014
- Type: Text , Journal article
- Relation: Respiratory Research Vol. 15, no. 1 (2014), p. 1-12
- Full Text:
- Reviewed:
- Description: Background: Pulmonary-delivered gene therapy promises to mitigate vaccine safety issues and reduce the need for needles and skilled personnel to use them. While plasmid DNA (pDNA) offers a rapid route to vaccine production without side effects or reliance on cold chain storage, its delivery to the lung has proved challenging. Conventional methods, including jet and ultrasonic nebulizers, fail to deliver large biomolecules like pDNA intact due to the shear and cavitational stresses present during nebulization.Methods: In vitro structural analysis followed by in vivo protein expression studies served in assessing the integrity of the pDNA subjected to surface acoustic wave (SAW) nebulisation. In vivo immunization trials were then carried out in rats using SAW nebulized pDNA (influenza A, human hemagglutinin H1N1) condensate delivered via intratracheal instillation. Finally, in vivo pulmonary vaccinations using pDNA for influenza was nebulized and delivered via a respirator to sheep.Results: The SAW nebulizer was effective at generating pDNA aerosols with sizes optimal for deep lung delivery. Successful gene expression was observed in mouse lung epithelial cells, when SAW-nebulized pDNA was delivered to male Swiss mice via intratracheal instillation. Effective systemic and mucosal antibody responses were found in rats via post-nebulized, condensed fluid instillation. Significantly, we demonstrated the suitability of the SAW nebulizer to administer unprotected pDNA encoding an influenza A virus surface glycoprotein to respirated sheep via aerosolized inhalation.Conclusion: Given the difficulty of inducing functional antibody responses for DNA vaccination in large animals, we report here the first instance of successful aerosolized inhalation delivery of a pDNA vaccine in a large animal model relevant to human lung development, structure, physiology, and disease, using a novel, low-power (<1 W) surface acoustic wave (SAW) hand-held nebulizer to produce droplets of pDNA with a size range suitable for delivery to the lower respiratory airways. © 2014 Rajapaksa et al.; licensee BioMed Central Ltd.
- Authors: Rajapaksa, Anushi , Ho, Jenny , Qi, Aaisha , Bischof, Robert , Nguyen, Tri-Hung , Tate, Michelle , Piedrafita, David , McIntosh, Michelle , Yeo, Leslie , Meeusen, Els , Coppel, Ross , Friend, James
- Date: 2014
- Type: Text , Journal article
- Relation: Respiratory Research Vol. 15, no. 1 (2014), p. 1-12
- Full Text:
- Reviewed:
- Description: Background: Pulmonary-delivered gene therapy promises to mitigate vaccine safety issues and reduce the need for needles and skilled personnel to use them. While plasmid DNA (pDNA) offers a rapid route to vaccine production without side effects or reliance on cold chain storage, its delivery to the lung has proved challenging. Conventional methods, including jet and ultrasonic nebulizers, fail to deliver large biomolecules like pDNA intact due to the shear and cavitational stresses present during nebulization.Methods: In vitro structural analysis followed by in vivo protein expression studies served in assessing the integrity of the pDNA subjected to surface acoustic wave (SAW) nebulisation. In vivo immunization trials were then carried out in rats using SAW nebulized pDNA (influenza A, human hemagglutinin H1N1) condensate delivered via intratracheal instillation. Finally, in vivo pulmonary vaccinations using pDNA for influenza was nebulized and delivered via a respirator to sheep.Results: The SAW nebulizer was effective at generating pDNA aerosols with sizes optimal for deep lung delivery. Successful gene expression was observed in mouse lung epithelial cells, when SAW-nebulized pDNA was delivered to male Swiss mice via intratracheal instillation. Effective systemic and mucosal antibody responses were found in rats via post-nebulized, condensed fluid instillation. Significantly, we demonstrated the suitability of the SAW nebulizer to administer unprotected pDNA encoding an influenza A virus surface glycoprotein to respirated sheep via aerosolized inhalation.Conclusion: Given the difficulty of inducing functional antibody responses for DNA vaccination in large animals, we report here the first instance of successful aerosolized inhalation delivery of a pDNA vaccine in a large animal model relevant to human lung development, structure, physiology, and disease, using a novel, low-power (<1 W) surface acoustic wave (SAW) hand-held nebulizer to produce droplets of pDNA with a size range suitable for delivery to the lower respiratory airways. © 2014 Rajapaksa et al.; licensee BioMed Central Ltd.
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