| 1. |
- Hughes, Rod, et al.
(författare)
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Frequent productive cough : Symptom burden and future exacerbation risk among patients with asthma and/or COPD in the NOVELTY study
- 2022
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Ingår i: Respiratory Medicine. - : Elsevier. - 0954-6111 .- 1532-3064. ; 200
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Persistent cough with sputum production is an important clinical trait in chronic obstructive pulmonary disease (COPD). We defined "frequent productive cough" based on 2 questions from the St George's Respiratory Questionnaire (SGRQ) and sought to determine its occurrence and associated outcomes in patients with physician-assigned asthma and/or COPD from the NOVELTY study. Methods: Frequent productive cough was defined as cough and sputum production most or several days/week for the past 3 months (scoring >= 3 for both SGRQ questions). Relationships with baseline disease characteristics and exacerbations over 12 months' follow-up were examined using logistic regression. Results: Baseline SGRQ data were available for 7125 patients, of whom 31.3% had frequent productive cough. It was more common in asthma + COPD (38.8%) and COPD (38.1%) than asthma (25.0%), increasing with physician-assessed severity, and in current versus former and never smokers. Patient-reported symptomatic worsening was more common in patients with versus without frequent productive cough. Reduced post-bronchodilator FEV1 (odds ratio [OR] per 10% decrement 1.14 [95% confidence interval 1.11-1.16]) and history of pollutant exposure at home/work (OR 1.50 [1.33-1.69]) were associated with frequent productive cough in all diagnoses. Patients with baseline frequent productive cough were more likely to have >= 1 exacerbation over the subsequent 12 months (OR 1.71 [1.52-1.93]), including exacerbations requiring hospital admission and those treated with oral corticosteroids. Conclusions: Frequent productive cough represents an important indicator of adverse clinical outcomes across asthma and/or COPD. Research into the underlying pathologic mechanisms is required to support targeted therapy development.
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| 2. |
- Johansson, S., et al.
(författare)
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Low levels of CC16 in nasal fluid of children with birch pollen-induced rhinitis
- 2005
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Ingår i: Allergy. - : Wiley. - 0105-4538 .- 1398-9995. ; 60:5, s. 638-42
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Clara cell protein 16 (CC16; secretoglobin 1A1) is an anti-inflammatory protein mainly expressed in the epithelial cells in the airways. OBJECTIVE: To compare the levels of CC16 in nasal lavage (NAL) from children with intermittent allergic rhinitis and healthy controls and to study the effect of a local steroid. METHODS: Thirty schoolchildren with birch pollen allergy and 30 healthy controls from the same schools were included in the study. The NAL fluid was collected before the season, during the birch pollen season and, for the patients, after 1 week of treatment with a local steroid. Symptom scores were obtained on every occasion. CC16 and eosinophil cationic protein (ECP) were analyzed with enzyme-linked immunosorbent assay. RESULTS: The nasal fluid levels of CC16 were significantly lower in patients than in controls, before and during pollen season. Before the season, the median CC16 concentrations were 9.1 (range 1.1-117) microg/l in patients and 25.7 (6.1-110.2) microg/l in controls. During the season, the median CC16 concentrations in nasal fluid were 12.9 (2.3-89.7) microg/l in the allergic children and 22.0 (9.5-90.1) microg/l in the healthy controls (P = 0.0005). Symptom scores, nasal fluid eosinophils and ECP were higher in patients during the season. Treatment with a local steroid did not change the CC16 levels. CONCLUSIONS: Nasal fluid CC16 levels were lower in children with birch pollen-induced allergic rhinitis than in healthy controls both before and during the pollen season. We speculate that reduction in anti-inflammatory activity by CC16 may contribute to the pathogenesis of allergic rhinitis.
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| 3. |
- Karlsson, Niklas, et al.
(författare)
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Validation of a diagnosis-agnostic symptom questionnaire for asthma and/or COPD
- 2021
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Ingår i: ERJ Open Research. - : European Respiratory Society. - 2312-0541. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Background he Respiratory Symptoms Questionnaire (RSQ) is a novel, 4-item patient-reported diagnosis-agnostic tool designed to assess the frequency of respiratory symptoms and their impact on activity, without specifying a particular diagnosis. Our objective was to examine its validity in patients with asthma and/or chronic obstructive pulmonary disease (COPD).Methods Baseline data were randomly sampled from patients who completed the RSQ in the NOVELTY study (NCT02760329). The total sample (N=1530) comprised three randomly selected samples (N=510 each) from each physician-assigned diagnostic group (asthma, asthma+COPD, COPD). The internal consistency and structural validity of the RSQ were evaluated using exploratory and confirmatory factor analyses; psychometric performance was observed using Classical Test Theory and Item Response Theory analyses.Results For the total sample, the mean RSQ score was 5.6 (sd 4.3; range: 0–16). Irrespective of diagnosis, the internal consistency of items was uniformly adequate (Cronbach's alphas range: 0.76–0.80). All items had high factor loadings, and structural characteristics of the measure were invariant across groups. Using the total sample, RSQ items informatively covered the theta score range of –2.0 to 2.8, with discrimination coefficients for individual items being high-to-very high (1.7–2.6). Strong convergent correlations were observed between the RSQ and St George's Respiratory Questionnaire (SGRQ; 0.77, p<0.001).Conclusions he RSQ is a valid, brief, patient-reported tool for assessing respiratory symptoms in patients across the whole spectrum of asthma and/or COPD, rather than using different questionnaires for each diagnosis. It can be used for monitoring respiratory symptoms in clinical practice, clinical trials and real-world studies.
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| 4. |
- Keen, Christina, et al.
(författare)
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Airway nitric oxide in patients with cystic fibrosis is associated with pancreatic function, Pseudomonas infection, and polyunsaturated fatty acids.
- 2007
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Ingår i: Chest. - : Elsevier BV. - 0012-3692. ; 131:6, s. 1857-64
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Airway nitric oxide (NO) is low or normal in cystic fibrosis (CF) patients. This may affect bacterial status since NO has antimicrobial properties. Arachidonic acid (AA), which is increased in the serum and airways of CF patients, has been shown to reduce NO levels. The aim of this study was to investigate whether airway NO level correlates with genotype and pancreatic function, and whether low airway NO level is associated with bacterial infection and increased serum AA level in CF patients. METHOD: Nasal NO (nNO) and exhaled NO (eNO) were measured according to the European Respiratory Society/American Thoracic Society standard in 59 CF patients aged 7 to 55 years, 80% of whom were pancreatic insufficient (PI) and 51% were chronically infected with Pseudomonas aeruginosa. RESULTS: PI CF patients had significantly lower nNO levels than pancreatic-sufficient (PS) patients. Airway NO level did not correlate with lung function or inflammatory parameters. PI patients chronically infected with P aeruginosa had significantly lower nNO levels than noninfected PI patients. nNO level correlated inversely with the AA/docosahexaenoic acid ratio, and eNO with the essential fatty acid (FA) deficiency index, which is the ratio between mead acid and AA. CONCLUSIONS: CF patients with PI, which is associated with more severe genotypes, had lower airway NO levels than patients with PS. Low NO level was correlated to chronic P aeruginosa infection, and an association was found between airway NO level and the abnormal serum phospholipid FA pattern.
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| 5. |
- Keen, Christina, et al.
(författare)
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Bet v 1-specific IgA increases during the pollen season but not after a single allergen challenge in children with birch pollen-induced intermittent allergic rhinitis
- 2005
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Ingår i: Pediatr Allergy Immunol. - : Wiley-Blackwell. - 0905-6157 .- 1399-3038. ; 16:3, s. 209-16
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Tidskriftsartikel (refereegranskat)abstract
- Allergen-specific immunoglobulins of the Immunoglobulin A (IgA) type have been found in the nasal fluid of patients with allergic rhinitis. IgA may play a protective role, but there are also data which show that allergen-specific IgA can induce eosinophil degranulation. The aim of this study was to quantitate Bet v 1-specific IgA in relation to total IgA in the nasal fluid of children with birch pollen-induced intermittent allergic rhinitis and healthy controls, after allergen challenge and during the natural pollen season. Eosinophil cationic protein (ECP), Bet v 1-specific IgA and total IgA were analyzed in nasal fluids from 30 children with birch pollen-induced intermittent allergic rhinitis and 30 healthy controls. Samples were taken before the pollen season, after challenge with birch pollen and during the pollen season, before and after treatment with nasal steroids. During the pollen season, but not after nasal allergen challenge, Bet v 1-specific IgA increased in relation to total IgA in children with allergic rhinitis. No change was found in the healthy controls. The ratio of Bet v 1-specific IgA to total IgA increased from 0.1 x 10(-3) (median) to 0.5 x 10(-3) in the allergic children, p < 0.001. No change was seen after treatment with nasal steroids, although symptoms, ECP and eosinophils were reduced. In conclusion, allergen-specific IgA in relation to total IgA increases in nasal fluids during the pollen season in allergic children but not in healthy controls. These findings are compatible with the hypothesis that allergen-specific IgA plays a role in the allergic inflammation and further studies are needed to clarify the functional role of these allergen-specific antibodies.
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| 6. |
- Keen, Christina
(författare)
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Exahaled NO and small airway function in asthma and cystic fibrosis
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Asthma and cystic fibrosis (CF) are chronic inflammatory airway disorders known to involve the peripheral airways. Non-invasive tests sensitive to peripheral airway function and inflammation are therefore of high priority. Multiple breath inert gas washout (MBW) is a test sensitive to small airway function and exhaled nitric oxide (NO) reflects airway inflammation in asthma. Aim: To use exhaled NO in combination with MBW to assess the contribution of small airway inflammation and dysfunction in paediatric asthma and CF in order to potentially allow for earlier intervention and more successful management of these conditions in the future. Results: CF subjects had reduced levels of nasal and exhaled NO. All but three children with CF had abnormally elevated LCI. Low levels of NO were associated with impaired airway function, chronic infection with Ps. Aeruginosa, severe genotypes and the fatty acid deficiency characteristic for CF subjects. Low levels of alveolar NO, albeit not lower in CF than in healthy controls, were associated with increased systemic inflammation and chronic bacterial airway colonisation. LCI, Scond, and Sacin were all significantly elevated in children with asthma and Scond was the marker that most significantly differentiated the asthmatic children from the healthy controls. Increased Scond was associated with increased levels of exhaled NO and airway hyper-responsiveness and Sacin correlated with alveolar NO. Conclusions: This thesis provides further evidence of small airway involvement in both paediatric asthma and CF. The findings of clinically significant dysfunction of the small conducting airways in paediatric asthma and the associations between small airway dysfunction, increased levels of exhaled NO and airway hyper-responsiveness are novel findings. In CF, low levels of exhaled NO are linked to small airway dysfunction. These findings provide new exciting insights into the pathology and pathophysiology of paediatric asthma and CF and may allow for earlier and better targeted interventions.
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| 7. |
- Keen, Christina, et al.
(författare)
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Low levels of exhaled nitric oxide are associated with impaired lung function in cystic fibrosis.
- 2010
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Ingår i: Pediatric pulmonology. - : Wiley. - 1099-0496 .- 8755-6863. ; 45:3, s. 241-8
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Tidskriftsartikel (refereegranskat)abstract
- Fraction of exhaled nitric oxide (FENO) is often reduced in cystic fibrosis (CF). FENO at different expiratory flows can provide an indication of the site of nitric oxide production. The aim of this study was to examine whether NO parameters are related to overall (FEV(1)) or peripheral (lung clearance index, LCI, measured by multiple breath SF(6) washout) airway function and systemic inflammation in CF. Secondary aim was to compare alveolar NO and bronchial NO flux calculated by two different mathematical models, a linear and a nonlinear method. Thirty-five healthy and 45 CF children were recruited. FENO at 50 ml/sec (FENO(50)) and bronchial NO flux were lower in CF than controls, 9.5 (2.7-38.8) (median (range)) versus 12.4 (5.2-40.1) ppb, P = 0.029, and 391 (97-1772) versus 578 (123-1993) (pl/sec), P = 0.036, respectively. No difference in alveolar NO was shown. The nonlinear method resulted in lower alveolar NO and higher bronchial flux, than the linear method, but the result was closely correlated in both groups. LCI was higher in CF than controls, 8.4 (6.5-12.9) versus 5.9 (5.1-7.8), P < 0.001. FENO(50) was negatively correlated with LCI (r = -0.43; P = 0.003) and positively correlated with FEV(1) (r = 0.42, P = 0.004) in CF. Alveolar NO correlated negatively with inflammatory markers: orosomucoid (r = -0.42, P = 0.005), platelets (r = -0.50, P < 0.001) and white blood cell count (r = -0.48, P = 0.001). In conclusion, FENO(50) and bronchial NO flux are reduced in young CF subjects and low FENO(50) is associated with overall and small airway obstruction. NO parameters derived from the different models were closely related but the values differed slightly.
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| 8. |
- Keen, Christina, et al.
(författare)
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Small airway function, exhaled NO and airway hyper-responsiveness in paediatric asthma.
- 2011
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Ingår i: Respiratory medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Asthma is a chronic inflammatory airway disorder known to involve the peripheral airways. Current guidelines state that diagnosis and treatment should be guided by symptoms and spirometry. FEV(1) is, however, a poor marker of small airway function and correlates poorly with asthma control and airway inflammation. AIMS: To assess the contribution of small airway dysfunction and inflammation in paediatric asthma. A secondary aim was to study the associations between small airway dysfunction, airway inflammation and airway hyper-responsiveness (AHR). METHODS: Small airway function was measured as LCI, S(cond) and S(acin), evaluated with the SF(6) multiple breath inert gas washout (MBW) technique, in 47 asthmatic children and 74 healthy controls. Exhaled NO at multiple exhalation flow rates including 50mL/s (FENO(50)) was assessed to calculate alveolar NO and bronchial NO flux (a surrogate for airway inflammation). AHR was evaluated with isocapnoic dry air hyperventilation challenge in the asthmatic children. RESULTS: S(cond) was elevated in 31 (66%) and S(acin) in 18 (38%) of the asthmatic subjects. LCI was increased and FEV(1) decreased in 7 (15%) of the subjects with asthma. Individuals with AHR had higher S(cond) (p=0.001) and FENO(50) (p<0.0001) than those without AHR. The levels of FENO(50) and bronchial NO flux were elevated in asthmatic subjects compared with healthy controls. In asthma, S(cond) correlated with FENO(50) (r(s)=0.42, p=0.003) and alveolar NO (r(s)=0.40, p=0.011), and S(acin) correlated with alveolar NO (r(s)=0.40, p=0.015). CONCLUSION: Dysfunction of small conducting airways is associated with airway inflammation and hyper-responsiveness in paediatric asthma.
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| 9. |
- Keen, Christina, et al.
(författare)
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Supplementation With Fatty Acids Influences the Airway Nitric Oxide and Inflammatory Markers in Patients With Cystic Fibrosis
- 2010
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Ingår i: Journal of Pediatric Gastroenterology and Nutrition - JPGN. - 0277-2116 .- 1536-4801. ; 50:5, s. 537-544
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To obtain a balance in the fatty acid (FA) metabolism is important for the inflammatory response and of special importance in cystic fibrosis (CF), which is characterized by impaired FA metabolism, chronic inflammation, and infection in the airways. Nitric oxide (NO) has antimicrobial properties and low nasal (nNO) and exhaled NO (FENO), commonly reported in CF that may affect bacterial status. The present study investigates the effect of different FA blends on nNO and FENO and immunological markers in patients with CF. Patients and Methods: Forty-three patients with CF and "severe" mutations were consecutively enrolled in a randomized double-blind placebo-controlled study with 3 FA blends containing mainly n-3 or n-6 FA or saturated FA acting as placebo. FENO, nNO, serum phospholipid concentrations of FA, and biomarkers of inflammation were measured before and after 3 months of supplementation. Results: Thirty-five patients in clinically stable condition completed the study. The serum phospholipid FA pattern changed significantly in all 3 groups. An increase of the n-6FA, arachidonic acid, was associated with a decrease of FENO and nNO. The inflammatory biomarkers, erythrocyte sedimentation rate, and interleukin-8 decreased after supplementation with n-3 FA and erythrocyte sedimentation rate increased after supplementation with n-6 FA. Conclusions: This small pilot study indicated that the composition of dietary n-3 and n-6 FA influenced the inflammatory markers in CF. FENO and nNO were influenced by changes in the arachidonic acid concentration, supporting previous studies suggesting that both the lipid abnormality and the colonization with Pseudomonas influenced NO in the airways.
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| 10. |
- Reddel, Helen K, et al.
(författare)
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Prospective observational study in patients with obstructive lung disease : NOVELTY design
- 2019
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Ingår i: ERJ open research. - : European Respiratory Society (ERS). - 2312-0541. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Asthma and chronic obstructive pulmonary disease (COPD) have overlapping clinical features and share pathobiological mechanisms but are often considered distinct disorders. Prospective, observational studies across asthma, COPD and asthma-COPD overlap are limited. NOVELTY is a global, prospective observational 3-year study enrolling ∼12 000 patients ≥12 years of age from primary and specialist clinical practices in 19 countries (ClinicalTrials.gov identifier: NCT02760329). NOVELTY's primary objectives are to describe patient characteristics, treatment patterns and disease burden over time, and to identify phenotypes and molecular endotypes associated with differential outcomes over time in patients with a diagnosis/suspected diagnosis of asthma and/or COPD. NOVELTY aims to recruit real-world patients, unlike clinical studies with restrictive inclusion/exclusion criteria. Data collected at yearly intervals include clinical assessments, spirometry, biospecimens, patient-reported outcomes (PROs) and healthcare utilisation (HCU). PROs and HCU will also be collected 3-monthly via internet/telephone. Data will be used to identify phenotypes and endotypes associated with different trajectories for symptom burden, clinical progression or remission and HCU. Results may allow patient classification across obstructive lung disease by clinical outcomes and biomarker profile, rather than by conventional diagnostic labels and severity categories. NOVELTY will provide a rich data source on obstructive lung disease, to help improve patient outcomes and aid novel drug development.
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| 11. |
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