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BACKGROUND: People with interstitial lung disease (ILD) were deemed more vulnerable to the SARS-CoV-2 virus and isolated as a means of reducing risk of infection. This study examined the impact of the pandemic on daily life, psychological wellbeing and access to healthcare and identified approaches undertaken to remain safe. METHODS: Four specialist clinics in tertiary centres in Australia (Victoria: two sites; New South Wales: one site; Western Australia: one site) recruited patients with ILD during an 8-week period from March 2021. Semi-structured telephone interviews were conducted with transcripts analysed using principles of grounded theory. RESULTS: Ninety participants were interviewed between April and December 2021. Participants were predominantly female, former smokers with an average age of 66 years. IPF and connective tissue-ILD being the most common subtypes. Five main themes were identified: vulnerability reduced social interaction and isolation, access to healthcare services and support, staying active, emotional and psychological impact. Self-management strategies included staying active both physically and mentally. DISCUSSION: Self-management was key to managing the impact of the pandemic. In combination with advances in technology, implementation of strategies for monitoring wellbeing and support for self-management provides an opportunity to leverage the lessons learnt to ensure a more individualised model of care for people with ILD.
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COVID-19 , Enfermedades Pulmonares Intersticiales , Automanejo , Humanos , Femenino , Anciano , Masculino , COVID-19/epidemiología , SARS-CoV-2 , PandemiasRESUMEN
INTRODUCTION: The COVID-19 pandemic resulted in a rapid transformation of health services. This study aimed to understand the experiences of healthcare by people with interstitial lung disease (ILD), to inform future service delivery. METHODS: Four specialist clinics in tertiary centres in Australia (Victoria:2 sites; New South Wales: 1 site; Western Australia: 1 site) recruited patients with ILD during an 8-week period from March 2021. Participants completed a COVID-specific questionnaire focused on health-related experiences during 2020. RESULTS: Ninety nine (65% of 153) participants completed the questionnaire. 47% had idiopathic pulmonary fibrosis or connective tissue disease-associated ILD, 62% were female and the average age was 66 years. Whilst 56% rated their overall health in 2020 as the same as months prior, 38% indicated a worsening in health attributed to reduced physical activity and fear of contracting the virus. Access to healthcare professionals was 'good' in 61%, and 'fair-to-poor' for 37% due to missed respiratory assessments, with telehealth (mainly telephone) being perceived as less effective. 89% had contact with respiratory physicians, 68% with general practitioners, predominantly via telephone, with few video consultations. High satisfaction with care was reported by 78%, with lower satisfaction attributed to delays in assessments, disruption to usual services such as pulmonary rehabilitation, and dissatisfaction with telehealth. CONCLUSION: People with ILD were generally satisfied with their care during 2020, however reduced access to healthcare professionals was challenging for those experiencing a deterioration in health. Telehealth was largely well received but did not always meet the needs of people with ILD particularly when unwell.
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COVID-19 , Fibrosis Pulmonar Idiopática , Enfermedades Pulmonares Intersticiales , Telemedicina , Humanos , Femenino , Anciano , Masculino , Pandemias , Enfermedades Pulmonares Intersticiales/terapia , Fibrosis Pulmonar Idiopática/terapia , Telemedicina/métodosRESUMEN
Introduction: Idiopathic pulmonary fibrosis (IPF) is a progressively fibrotic lung condition with poor prognosis. Matrix metalloproteinase-7 (MMP7) is a protein secreted by epithelial cells in IPF lungs. It is not known if MMP7 expression correlates with fibrotic changes in lung tissue. Methods: Tissue samples from lung apices and bases were obtained from 20 IPF patients and 14 non-diseased control (NDC) donors. In formalin-fixed paraffin-embedded sections, histological assessment of fibrosis was performed; overall MMP7 positivity was assessed by immunohistochemistry and MMP7+ cells were quantified using multiplex immunohistochemistry. Protein expression of MMP7 in whole lung lysates was quantified by Western blotting. Bulk tissue transcriptomic profiles of 101 samples were analysed using RNA sequencing technologies. Results: Lung tissue from IPF bases was more fibrotic than in apices. MMP7 protein is elevated in IPF lung base tissue. In IPF whole lung lysates, MMP7 protein levels are increased compared to NDC donors and was increased in IPF lung bases compared to apices. MMP7 protein levels correlated with MMP7 gene expression levels in lung tissue. MMP7 transcript levels were increased in IPF base compared to NDC base lung tissue and increased in IPF base tissue compared to IPF apex tissue. Conclusions: Our cross-sectional study suggests that lung epithelial MMP7 expression increases as the tissue becomes more fibrotic and identifies a potentially nonepithelial or immune-cell source. Mechanisms of disease progression in IPF are still unclear, and our study suggests aberrant MMP7 production may be a histological starting point of lung tissue fibrosis.
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The mechanisms driving idiopathic pulmonary fibrosis (IPF) remain undefined, however it is postulated that coagulation imbalances may play a role. The impact of blood-derived clotting factors, including factor XII (FXII) has not been investigated in the context of IPF. Plasma levels of FXII were measured by ELISA in patients with IPF and in age-matched healthy donors. Expression of FXII in human lung tissue was quantified using multiplex immunohistochemistry and Western blotting. Mechanistic investigation of FXII activity was assessed in vitro on primary lung fibroblasts using qPCR and specific receptor/FXII inhibition. The functional outcome of FXII on fibroblast migration was examined by high-content image analysis. Compared with 35 healthy donors, plasma levels of FXII were not higher in patients with IPF (n = 27, P > 0.05). Tissue FXII was elevated in IPF (n = 11) and increased numbers of FXII+ cells were found in IPF (n = 8) lung tissue compared with nondiseased controls (n = 6, P < 0.0001). Activated FXII induced IL6 mRNA and IL-6 protein in fibroblasts that was blocked by anti-FXII antibody, CSL312. FXII induced IL-6 production via PAR-1 and NF-κB. FXII induced migration of fibroblasts in a concentration-dependent manner. FXII is normally confined to the circulation but it leaks from damaged vessels into the lung interstitium in IPF where it 1) induces IL-6 production and 2) enhances migration of resident fibroblasts, critical events that drive chronic inflammation and therefore, contribute to fibrotic disease progression. Targeting FXII-induced fibroblastic processes in IPF may ameliorate pulmonary fibrosis.
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Fibrosis Pulmonar Idiopática , Factor XII/metabolismo , Fibroblastos/metabolismo , Humanos , Fibrosis Pulmonar Idiopática/metabolismo , Interleucina-6/metabolismo , Pulmón/metabolismoRESUMEN
OBJECTIVE: People with pulmonary fibrosis (PF) consider self-management essential for maintaining health. This study aims to explore the needs and expectations of PF self-management from the patient and healthcare professionals (HCPs) perspectives. METHODS: Semi-structured interviews were conducted with people with PF and HCPs. Purposive sampling was used to recruit participants. Thematic analysis was performed using the principles of grounded theory. RESULTS: 18 individuals with PF and 15 HCPs were interviewed. Common self-management components reported included exercise, nutrition, maintaining healthy mind, avoiding infections, recognising deterioration and seeking help, managing symptoms and treatments, social support, and end-of-life planning. Both groups felt that effective self-management required individualised strategies, supports, and reliable information. People with PF identified access to personal health data and self-acceptance as part of self-management. HCPs highlighted the importance of accessible supports and managing patient expectations of disease course and treatments. Some HCPs concerned about missed detection of deterioration and suggested that self-management strategies for PF may differ to other lung diseases. CONCLUSION: This study identified components important for self-management in PF and provides a basis for designing a PF self-management package. PRACTICE IMPLICATIONS: Self-management of PF can be facilitated with individualised support from HCPs and reliable information that is accessible.
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Fibrosis Pulmonar , Automanejo , Atención a la Salud , Personal de Salud , Humanos , Fibrosis Pulmonar/terapia , Investigación CualitativaRESUMEN
Objectives: The objectives of this study were to determine the proportion of patients with interstitial lung disease (ILD) referred to pulmonary rehabilitation (PR) and to understand their experiences of participation or non-participation. Methods: Adults (>18 years old) with a diagnosis of ILD were identified from the Alfred Health ILD registry in Melbourne. Information regarding PR referral and attendance were collected from medical records. Semi-structured interviews with open-ended questions were conducted with patients who had been referred to PR. Results: Of 336 patients eligible for inclusion, PR referral was identified in 137 patients (40.7%). Patients referred to PR had worse respiratory function than those not referred (forced vital capacity mean 64 (SD 23) vs 79 (19) % predicted) and more desaturation during a 6-min walk test (86.6 (7.8%) vs 88.5 (7.0%)). Semi-structured interviews identified three major themes: valued components of PR (supervision and individualization, improved confidence with exercise, education and peer support); limited knowledge about PR prior to attendance and barriers to attending PR (lack of perceived benefits, fear of exercise and accessibility). Discussion: Over 40% of patients who attended a specialist ILD clinic were referred to pulmonary rehabilitation, with higher referral rates in those with more severe disease. There are opportunities to improve patient knowledge regarding the role and expected benefits of PR in people with ILD.
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Enfermedades Pulmonares Intersticiales , Enfermedad Pulmonar Obstructiva Crónica , Adolescente , Tolerancia al Ejercicio , Humanos , Enfermedades Pulmonares Intersticiales/rehabilitación , Enfermedades Pulmonares Intersticiales/terapia , Evaluación del Resultado de la Atención al Paciente , Enfermedad Pulmonar Obstructiva Crónica/terapia , Derivación y Consulta , Prueba de PasoRESUMEN
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease of unknown etiology and poor prognosis. In IPF, aberrant extracellular matrix production by activated, hyperproliferative fibroblasts drives disease progression but the exact mechanisms by which this occurs remains undefined. The transcription factor nuclear factor kappa-B (NF-ĸB) has been suggested as a potential therapeutic target in IPF and therefore the aim of this study was to investigate the efficacy of ACT001, an NF-ĸB inhibitor, on primary fibroblasts derived from patients with and without IPF. Primary lung fibroblasts derived from eight patients with IPF and eight age-matched non-diseased controls (NDC) were treated with 0-10 µM ACT001 and the effects on fibroblast activity (viability and proliferation, fibroblast-to-myofibroblast transition, fibronectin expression), interleukin (IL)-6 and IL-8 cytokine release were quantified. ACT001 inhibited fibroblast activity in a concentration-dependent manner in both groups of fibroblasts. ACT001 inhibited IL-6 but not IL-8 production in unstimulated fibroblasts. ACT001 is a water-soluble compound with a stable half-life in plasma, thus making it an attractive candidate for further investigation as a therapeutic in IPF. This study adds to the growing body of literature that demonstrates anti-fibrotic activity of NF-ĸB inhibition in the context of IPF.
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Fibroblastos/efectos de los fármacos , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , FN-kappa B/antagonistas & inhibidores , Sesquiterpenos/uso terapéutico , Adulto , Anciano , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Relación Dosis-Respuesta a Droga , Femenino , Fibroblastos/metabolismo , Fibroblastos/patología , Humanos , Fibrosis Pulmonar Idiopática/metabolismo , Fibrosis Pulmonar Idiopática/patología , Masculino , Persona de Mediana Edad , FN-kappa B/metabolismo , Sesquiterpenos/química , Sesquiterpenos/farmacologíaRESUMEN
Pulmonary complications in CTD are common and can involve the interstitium, airways, pleura and pulmonary vasculature. ILD can occur in all CTD (CTD-ILD), and may vary from limited, non-progressive lung involvement, to fulminant, life-threatening disease. Given the potential for major adverse outcomes in CTD-ILD, accurate diagnosis, assessment and careful consideration of therapeutic intervention are a priority. Limited data are available to guide management decisions in CTD-ILD. Autoimmune-mediated pulmonary inflammation is considered a key pathobiological pathway in these disorders, and immunosuppressive therapy is generally regarded the cornerstone of treatment for severe and/or progressive CTD-ILD. However, the natural history of CTD-ILD in individual patients can be difficult to predict, and deciding who to treat, when and with what agent can be challenging. Establishing realistic therapeutic goals from both the patient and clinician perspective requires considerable expertise. The document aims to provide a framework for clinicians to aid in the assessment and management of ILD in the major CTD. A suggested approach to diagnosis and monitoring of CTD-ILD and, where available, evidence-based, disease-specific approaches to treatment have been provided.
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Enfermedades del Tejido Conjuntivo/complicaciones , Enfermedades del Tejido Conjuntivo/diagnóstico , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/diagnóstico , Sociedades Médicas , Australia , Ensayos Clínicos como Asunto , Enfermedades del Tejido Conjuntivo/diagnóstico por imagen , Enfermedades del Tejido Conjuntivo/patología , Humanos , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/patología , Nueva ZelandaRESUMEN
BACKGROUND: CXCR4, a transmembrane-receptor located on epithelial cells that is activated by CXCL12, may have a role in IPF via migration of CXCR4+ fibrocytes to the lung. However, its expression has not been fully characterised in idiopathic pulmonary fibrosis (IPF) or other fibrotic interstitial lung diseases (ILDs). CXCL12 is constitutively expressed in the bone marrow, and levels of CXCR4 regulate control of this signalling pathway. The aim of this study was to profile the expression of CXCR4 in lung tissue and peripheral circulation of patients with IPF and other fibrotic ILDs. METHODS: Expression of CXCR4 on peripheral blood mononuclear cells (PBMCs) was examined by flow cytometry in 20 patients with IPF and 10 age-matched non-disease control (NDC) donors. Levels of CXCL12 in human plasma were measured by ELISA. Expression of CXCR4, CXCL12, CD45, and e-cadherin was assessed in IPF (n = 10), other fibrotic ILD (n = 8) and NDC (n = 10) lung tissue by multiplex immunohistochemistry (OPAL) and slides were scanned using a Vectra 3 scanner. Cells were quantified with computer automated histological analysis software (HALO). RESULTS: In blood, the number of CXCR4+ cells was lower but the level of CXCL12 was higher in patients with IPF compared to NDC donors. Elevated CXCR4 expression was detected in lung tissue from patients with IPF and other fibrotic ILDs compared to NDC. There were higher levels of CXCR4+/e-cadherin+/CXCL12+ (epithelial) cells in IPF lung tissue compared to NDC, but there was no difference in the numbers of CXCR4+/CD45+/CXCL12+ (myeloid) cells between the two groups. CONCLUSIONS: This report demonstrates that CXCR4 is overexpressed not only in IPF but also in other ILDs and expression is particularly prominent within both honeycomb cysts and distal airway epithelium. This observation supports the hypothesis that CXCR4 may drive tissue fibrosis through binding its specific ligand CXCL12. Although CXCR4 expressing cells could be either of epithelial or myeloid origin it appears that the former is more prominent in IPF lung tissue. Further characterization of the cells of the honeycomb cyst may lead to a better understanding of the fibrogenic processes in IPF and other end-stage fibrotic ILDs.
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Fibrosis Pulmonar Idiopática/sangre , Fibrosis Pulmonar Idiopática/diagnóstico , Pulmón/metabolismo , Pulmón/patología , Receptores CXCR4/sangre , Anciano , Biomarcadores/sangre , Femenino , Humanos , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/patología , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND AND OBJECTIVE: Ambulatory oxygen therapy is often provided to patients with interstitial lung disease (ILD). Lightweight portable oxygen concentrators (POCs) provide an alternative to traditional portable systems such as compressed oxygen cylinders; however, their efficacy in patients with ILD has not been assessed. This study aimed to evaluate the clinical performance of three ambulatory oxygen systems (two different POCs and a compressed oxygen cylinder) during 6-min walk tests (6MWTs) in patients with ILD and exertional desaturation. METHODS: A total of 20 participants with ILD of varying aetiologies who demonstrated exertional desaturation to <90% on room air during 6MWT were recruited. Each participant performed two 6MWTs while breathing room air. On a subsequent day, two further 6MWTs were performed, in random order: one breathing oxygen via a POC (either the Inogen One G2 POC or the EverGo POC at the setting of 6) and one with a compressed oxygen cylinder (at 5 L/min). RESULTS: There were no significant differences in nadir oxygen saturation (SpO2 ) during 6MWTs using different portable oxygen devices (Trial 1: mean SpO2 for Inogen One G2 POC: 82.3 ± 3.5% vs oxygen cylinder: 80.3 ± 2.2%, P = 0.14; Trial 2: mean SpO2 for EverGo POC: 85.7 ± 7.7% vs oxygen cylinder: 86.1 ± 6.1%, P = 0.79). The mean 6-min walk distances were not significantly different among the three devices. CONCLUSION: The performance of the Inogen One G2 POC and the EverGo POC had comparable performance with that of the compressed oxygen cylinder during walking in patients with ILD and exertional desaturation.
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Enfermedades Pulmonares Intersticiales/terapia , Terapia por Inhalación de Oxígeno , Oxígeno/análisis , Caminata/fisiología , Anciano , Atención Ambulatoria/métodos , Estudios Cruzados , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/fisiopatología , Masculino , Persona de Mediana Edad , Evaluación de Procesos y Resultados en Atención de Salud , Consumo de Oxígeno , Terapia por Inhalación de Oxígeno/instrumentación , Terapia por Inhalación de Oxígeno/métodos , Esfuerzo Físico/fisiologíaRESUMEN
BACKGROUND AND OBJECTIVE: Multidisciplinary discussions (MDDs) have been shown to improve diagnostic accuracy in interstitial lung disease (ILD) diagnosis. However, their clinical impact on patient care has never been clearly demonstrated. We describe the effect that an ILD multidisciplinary service has upon the diagnosis and management of patients with suspected ILD. METHODS: Patients at two specialized centres with suspected ILD underwent ILD multidisciplinary team review (ILD-MDT) (standard ILD clinic visit and diagnostic review at ILD-MDD). We compared changes in ILD diagnosis and management at referral to those following the ILD-MDT. RESULTS: Ninety patients, 60% males (54/90), aged 67.3 years (SD = 11.4) were reviewed for suspected ILD. Overall, the ILD-MDT resulted in a change in specific ILD diagnosis in 48/90 (53%) patients. Of the 27 patients referred with a diagnosis of idiopathic pulmonary fibrosis (IPF), the diagnosis was changed at MDD in 10 patients. In contrast, seven patients had their diagnosis changed to IPF. There was also a significant reduction in 'unclassifiable' diseases and disease behaviour classifications provided additional information beyond ILD diagnosis. CONCLUSION: Dedicated tertiary ILD-MDT service has an important clinical impact on the care of the ILD patient, with frequent changes in ILD diagnosis and subsequent management. Further research to investigate long-term clinical outcomes of ILD-MDT is required.
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Fibrosis Pulmonar Idiopática , Comunicación Interdisciplinaria , Enfermedades Pulmonares Intersticiales , Grupo de Atención al Paciente/organización & administración , Anciano , Australia , Manejo de la Enfermedad , Femenino , Humanos , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/terapia , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/terapia , Masculino , Persona de Mediana Edad , Mejoramiento de la Calidad , Derivación y Consulta/normas , Resultado del TratamientoRESUMEN
Pulmonary rehabilitation (PR) is recommended for people with interstitial lung disease (ILD); however, the educational content of PR was not designed for this group. This study explored the perspectives of patients and ILD clinicians regarding the educational content of PR for ILD. A qualitative study using individual semi-structured interviews was undertaken. Transcripts were coded independently by two investigators and themes established by consensus. Participants were 18 people with ILD (9 idiopathic pulmonary fibrosis, diffusing capacity for carbon monoxide 54 (20)% predicted) and 14 clinicians from 5 countries and 5 disciplines. Major themes from patient interviews were the importance of knowing what the future might bring and the need for honesty from clinicians. Most were happy to attend standard PR education sessions but wanted ILD-specific content. Patients wanted information about end-of-life planning and most were happy to discuss it in a group. Among clinicians, there was no consensus regarding whether prognosis should be discussed in PR. Most clinicians supported discussion of advanced care planning, however, some thought it should not be discussed in a group. We conclude that people with ILD have specific educational needs that may not be met in the current PR format. Patients and clinicians have some discordant views about programme content.
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Planificación Anticipada de Atención , Actitud Frente a la Salud , Enfermedades Pulmonares Intersticiales/rehabilitación , Educación del Paciente como Asunto/métodos , Relaciones Profesional-Paciente , Revelación de la Verdad , Anciano , Anciano de 80 o más Años , Actitud del Personal de Salud , Femenino , Humanos , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Investigación Cualitativa , Cuidado Terminal/métodosRESUMEN
BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) often presents with persistently uncontrolled asthma despite the use of corticosteroids and antifungal therapy. Omalizumab is a humanized anti-IgE monoclonal antibody currently used to treat severe asthma. OBJECTIVE: The aim was to assess the clinical and immunologic effects of omalizumab in ABPA in a randomized, placebo-controlled trial. METHODS: Patients with chronic ABPA were randomized to 4-month treatment with omalizumab (750 mg monthly) or placebo followed by a 3-month washout period in a cross-over design. The main endpoint was number of exacerbations. Other clinical endpoints included lung function, exhaled nitric oxide (FeNO), quality of life and symptoms. In vitro basophil activation to Aspergillus fumigatus extract and basophil FcεR1 and surface-bound IgE levels were assessed by flow cytometry. RESULTS: Thirteen patients were recruited with mean total IgE 2314 ± 2125 IU/mL. Exacerbations occurred less frequently during the active treatment phase compared with the placebo period (2 vs 12 events, P = .048). Mean FeNO decreased from 30.5 to 17.1 ppb during omalizumab treatment (P = .03). Basophil sensitivity to A. fumigatus and surface-bound IgE and FcεR1 levels decreased significantly after omalizumab but not after placebo. CONCLUSION: Omalizumab can be used safely to treat ABPA, despite high serum IgE levels. Clinical improvement was accompanied by decreased basophil reactivity to A. fumigatus and FcεR1 and surface-bound IgE levels.
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Antialérgicos/uso terapéutico , Aspergilosis Broncopulmonar Alérgica/tratamiento farmacológico , Omalizumab/uso terapéutico , Adulto , Anciano , Antialérgicos/farmacología , Antígenos Fúngicos/inmunología , Aspergilosis Broncopulmonar Alérgica/sangre , Aspergilosis Broncopulmonar Alérgica/inmunología , Aspergilosis Broncopulmonar Alérgica/fisiopatología , Aspergillus fumigatus/inmunología , Basófilos/efectos de los fármacos , Basófilos/inmunología , Estudios Cruzados , Femenino , Volumen Espiratorio Forzado , Humanos , Inmunoglobulina E/sangre , Masculino , Persona de Mediana Edad , Óxido Nítrico/metabolismo , Omalizumab/farmacología , Calidad de Vida , Receptores de IgE/inmunología , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVES: Little is known about the prevalence of anxiety in interstitial lung disease (ILD), and the contributors to depression are not clear. The aim of this study was to determine the prevalence and predictors of anxiety and depression in people with ILD. METHODS: One hundred and twenty-four individuals with ILD (age 64 years (standard deviation 12), 48 idiopathic pulmonary fibrosis) participated. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale to determine likely cases and borderline cases. Associations with demographic data, respiratory function, 6-min walk and Modified Medical Research Council Dyspnoea Scale (MMRC) were examined. RESULTS: The prevalence of anxiety was 31%, with clinically significant anxiety in 12%. Depression was present in 23% of individuals, with 7% having clinically significant depression. Independent predictors of anxiety were a higher MMRC score (P = 0.005, odds ratio (OR) for case 2.60, 95% confidence interval 1.37 to 4.92) and higher nadir SpO2 during walking (P = 0.003, OR for case 1.16, 1.04-1.30). Independent predictors of depression were a higher MMRC score (P = 0.006, case OR 3.84, 1.25-11.78, borderline case OR 2.44, 1.14-5.19) and a greater number of comorbidities (P = 0.003, case OR 2.02, 0.97-4.21, borderline case OR 2.26, 1.30-3.93). CONCLUSIONS: Anxiety and depression are present in a significant minority of individuals with ILD. Dyspnoea and comorbidities are important contributors that may be amenable to intervention.
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Ansiedad/epidemiología , Depresión/epidemiología , Disnea , Enfermedades Pulmonares Intersticiales , Calidad de Vida , Anciano , Australia/epidemiología , Comorbilidad , Disnea/fisiopatología , Disnea/psicología , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/epidemiología , Enfermedades Pulmonares Intersticiales/fisiopatología , Enfermedades Pulmonares Intersticiales/psicología , Masculino , Persona de Mediana Edad , Prevalencia , Medición de Riesgo , Factores de Riesgo , CaminataRESUMEN
BACKGROUND: Peanut allergy is a life-threatening condition; there is currently no cure. Although whole allergen extracts are used for specific immunotherapy for many allergies, they can cause severe reactions, and even fatalities, in peanut allergy. OBJECTIVE: This study aimed to identify short, T-cell epitope-based peptides that target allergen-specific CD4(+) T cells but do not bind IgE as candidates for safe peanut-specific immunotherapy. METHODS: Multiple CD4(+) T-cell lines specific for the major peanut allergen Ara h 2 were generated from PBMCs of 16 HLA-diverse subjects with peanut allergy by using 5,6-carboxyfluorescein diacetate succinimidylester-based methodology. Proliferation and ELISPOT assays were used to identify dominant epitopes recognized by T-cell lines and to confirm recognition by peripheral blood T cells of epitope-based peptides modified for therapeutic production. HLA restriction of core epitope recognition was investigated by using anti-HLA blocking antibodies and HLA genotyping. Serum-IgE peptide-binding was assessed by dot-blot. RESULTS: Five dominant CD4(+) T-cell epitopes were identified in Ara h 2. In combination, these were presented by HLA-DR, HLA-DP, and HLA-DQ molecules and recognized by T cells from all 16 subjects. Three short peptide variants containing these T-cell epitopes were designed with cysteine-to-serine substitutions to facilitate stability and therapeutic production. Variant peptides showed HLA-binding degeneracy, did not bind peanut-specific serum IgE, and could directly target T(H)2-type T cells in peripheral blood of subjects with allergy. CONCLUSION: Short CD4(+) T-cell epitope-based Ara h 2 peptides were identified as novel candidates for a T-cell-targeted peanut-specific immunotherapy for an HLA-diverse population.
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Albuminas 2S de Plantas/uso terapéutico , Antígenos de Plantas/uso terapéutico , Linfocitos T CD4-Positivos/efectos de los fármacos , Epítopos de Linfocito T/uso terapéutico , Glicoproteínas/uso terapéutico , Inmunoterapia , Hipersensibilidad al Cacahuete/terapia , Péptidos/uso terapéutico , Albuminas 2S de Plantas/genética , Adulto , Antígenos de Plantas/genética , Epítopos de Linfocito T/genética , Glicoproteínas/genética , Humanos , Péptidos/genética , Reproducibilidad de los ResultadosRESUMEN
Bahia grass, Paspalum notatum, is a clinically important subtropical grass with a prolonged pollination season from spring to autumn. We aimed to clone and characterise the major Bahia grass pollen allergen, Pas n 1. Grass pollen-allergic patients presenting to a tertiary hospital allergy clinic were tested for IgE reactivity with Bahia grass pollen extract by skin prick testing, ImmunoCAP, ELISA and immunoblotting. Using primers deduced from the N-terminal peptide sequence of a group 1 allergen of Bahia grass pollen extract separated by two-dimensional gel electrophoresis, the complete Pas n 1 cDNA was obtained by rapid amplification of cDNA ends and cloned. Biological relevance of recombinant Pas n 1 expressed in Escherichia coli was assessed by serum IgE reactivity and basophil activation. Twenty-nine of 34 (85%) consecutive patients presenting with grass pollen allergy were skin prick test positive to Bahia grass pollen. The Pas n 1 cDNA has sequence homology with the beta-expansin 1 glycoprotein family and is more closely related to the maize pollen group 1 allergen (85% identity) than to ryegrass Lol p 1 or Timothy grass Phl p 1 (64 and 66% identity, respectively). rPas n 1 reacted with serum IgE in 47 of 55 (85%) Bahia grass pollen-allergic patients, activated basophils and inhibited serum IgE reactivity with the 29 kDa band of Bahia grass pollen extract. In conclusion the cDNA for the major group 1 allergen of the subtropical Bahia grass pollen, Pas n 1, was identified and cloned. rPas n 1 is immunologically active and is a valuable reagent for diagnosis and specific immunotherapy of grass pollen allergy.