Exploring factors influencing asthma control and asthma-specific health-related quality of life among children

Background

Little is known about factors contributing to children’s asthma control status and health-related quality of life (HRQoL). The study objectives were to assess the relationship between asthma control and asthma-specific HRQoL in asthmatic children, and to examine the extent to which parental health literacy, perceived self-efficacy with patient-physician interaction, and satisfaction with shared decision-making (SDM) contribute to children’s asthma control and asthma-specific HRQoL.

Methods

This cross-sectional study utilized data collected from a sample of asthmatic children (n = 160) aged 8–17 years and their parents (n = 160) who visited a university medical center. Asthma-specific HRQoL was self-reported by children using the National Institutes of Health’s Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Asthma Impact Scale. Satisfaction with SDM, perceived self-efficacy with patient-physician interaction, parental health literacy, and asthma control were reported by parents using standardized measures. Structural equation modeling (SEM) was performed to test the hypothesized pathways.

Results

Path analysis revealed that children with better asthma control reported higher asthma-specific HRQoL (β = 0.4, P < 0.001). Parents with higher health literacy and greater perceived self-efficacy with patient-physician interactions were associated with higher satisfaction with SDM (β = 0.38, P < 0.05; β = 0.58, P < 0.001, respectively). Greater satisfaction with SDM was in turn associated with better asthma control (β = −0.26, P < 0.01).

Conclusion

Children’s asthma control status influenced their asthma-specific HRQoL. However, parental factors such as perceived self-efficacy with patient-physician interaction and satisfaction with shared decision-making indirectly influenced children’s asthma control status and asthma-specific HRQoL.     

Physiological relaxation induced by horticultural activity: transplanting work using flowering plants

Background

Despite increasing attention and a growing volume of research data, little physiological evidence is available on the benefits of horticultural activity and the different effects on individuals. Therefore, the aim of the present study was to investigate the physiological effects of horticultural activity and to examine how differences in personality alter these effects.

Results

The effects of transplanting real flowers (horticultural activity) and handling artificial flowers (control activity) on human physiological activity were compared. On the first day, eight participants engaged in horticultural activity and another eight in the control activity. On the second day, participants switched roles. Participants’ physiological conditions during each activity were assessed by measuring the heart rate and heart rate variability (HRV). Psychological responses, which were measured using a semantic differential rating scale, showed that the horticultural activity promoted comfortable, soothed, and natural feelings, compared to the control activity. Analysis of physiological responses using two-way repeated measures analysis of variance (ANOVA) revealed that sympathetic nervous activity significantly decreased in the late time period (11 to 15 minutes) of horticultural activity only in the type A group.

Conclusions

This study supports the fact that the horticultural activity can enhance psychological and physiological relaxation effects, although these physiological effects can differ among individuals with different personalities.     

Physiological and psychological responses of young males during spring-time walks in urban parks

Background

It is widely believed that contact with the natural environment can improve physical and mental health. Urban green spaces may provide city residents with these benefits; however, there is a lack of empirical field research on the health benefits of urban parks.

Methods

This field experiment was performed in May. Seventeen males aged 21.2 ± 1.7 years (mean ± standard deviation) were instructed to walk predetermined 15-minute courses in an urban park and a nearby city area (control). Heart rate and heart rate variability (HRV) were measured to assess physiological responses. The semantic differential (SD) method, Profile of Mood States (POMS), and State-Trait Anxiety Inventory (STAI) were used to measure psychological responses.

Results

Heart rate was significantly lower while walking in the urban park than while walking in the city street. Furthermore, the urban park walk led to higher parasympathetic nervous activity and lower sympathetic nervous activity compared with the walk through the city street. Subjective evaluations were generally in accordance with physiological reactions, and significantly higher scores were observed for the ‘comfortable’, ‘natural’, and ‘relaxed’ parameters following the urban park walk. After the urban park walk, the score for the ‘vigor’ subscale of the POMS was significantly higher, whereas that for negative feelings such as ‘tension-anxiety’ and ‘fatigue’ was significantly lower. The score for the anxiety dimension of the STAI was also significantly lower after the urban park walk.

Conclusions

Physiological and psychological results from this field experiment provide evidence for the physiological and psychological benefits of urban green spaces. A brief spring-time walk in an urban park shifted sympathetic/parasympathetic balance and improved mood state.     

Effects of 92% oxygen administration on cognitive performance and physiological changes of intellectually and developmentally disabled people

Background

The present study addressed how 92% oxygen administration affects cognitive performance, blood oxygen saturation (SpO₂), and heart rate (HR) of intellectually and developmentally disabled people.

Methods

Seven males (28.9 ± 1.8 years) and seven females (34.4 ± 8.3 years) with intellectual and developmental disabilities (disabled level 2.1 ± 0.5) completed an experiment consisting a 0-back task with normal air (21% oxygen) administered in one run and hyperoxic air (92% oxygen) administered in the other run. The experimental sequence in each run consisted of a 1-min adaptation phase, 2-min control phase, and 2-min 0-back task phase, where SpO₂ and HR were gauged for each phase.

Results

The administration of 92% oxygen increased 0-back task performance of intellectually and developmentally disabled people, in association with increased SpO₂ and decreased HR. Our results demonstrate that sufficient oxygen supply subserving cognitive functions, even as a short-term effect, could increase cognitive ability for the intellectually and developmentally disabled people.

Conclusions

It is concluded that enriched oxygen can positively affect, at least in the short-term, the working memory of those with intellectual and developmental disability.     

Computer quantification of airway collapse on forced expiration to predict the presence of emphysema

Background

Spirometric parameters are the mainstay for diagnosis of COPD, but cannot distinguish airway obstruction from emphysema. We aimed to develop a computer model that quantifies airway collapse on forced expiratory flow–volume loops. We then explored and validated the relationship of airway collapse with computed tomography (CT) diagnosed emphysema in two large independent cohorts.

Methods

A computer model was developed in 513 Caucasian individuals with ≥15 pack-years who performed spirometry, diffusion capacity and CT scans to quantify emphysema presence. The model computed the two best fitting regression lines on the expiratory phase of the flow-volume loop and calculated the angle between them. The collapse was expressed as an Angle of collapse (AC) which was then correlated with the presence of emphysema. Findings were validated in an independent group of 340 individuals.

Results

AC in emphysema subjects (N = 251) was significantly lower (131° ± 14°) compared to AC in subjects without emphysema (N = 223), (152° ± 10°) (p < 0.0001). Multivariate regression analysis revealed AC as best indicator of visually scored emphysema (R² = 0.505, p < 0.0001) with little significant contribution of K_CO, %predicted and FEV_1, %predicted to the total model (total R² = 0.626, p < 0.0001). Similar associations were obtained when using CT-automated density scores for emphysema assessment. Receiver operating characteristic (ROC) curves pointed to 131° as the best cut-off for emphysema (95.5% positive predictive value, 97% specificity and 51% sensitivity). Validation in a second group confirmed the significant difference in mean AC between emphysema and non-emphysema subjects. When applying the 131° cut-off, a positive predictive value of 95.6%, a specificity of 96% and a sensitivity of 59% were demonstrated.

Conclusions

Airway collapse on forced expiration quantified by a computer model correlates with emphysema. An AC below 131° can be considered as a specific cut-off for predicting the presence of emphysema in heavy smokers.     

Physiological and psychological effects of walking on young males in urban parks in winter

Background

Interaction with nature has a relaxing effect on humans. Increasing attention has been focused on the therapeutic effects of urban green space; however, there is a lack of evidence-based field research. This study provided scientific evidence supporting the physiological and psychological effects of walking on young males in urban parks in winter.

Findings

Subjects (13 males aged 22.5 ± 3.1 years) were instructed to walk predetermined 15-minute courses in an urban park (test) and in the city area (control). Heart rate and heart rate variability (HRV) were measured to assess physiological responses. The semantic differential (SD) method, Profile of Mood States (POMS), and State-Trait Anxiety Inventory (STAI) were used to determine psychological responses.Heart rate was significantly lower and the natural logarithm of the high frequency component of HRV was significantly higher when walking through the urban park than through the city area. The results of three questionnaires indicated that walking in the urban park improved mood and decreased negative feelings and anxiety.

Conclusions

Physiological and psychological data from this field experiment provide important scientific evidence regarding the health benefits of walking in an urban park. The results support the premise that walking in an urban park has relaxing effects even in winter.     

Sex differences in acetylcholine-induced sweating responses due to physical training

Purpose

The present study examined sex differences in the sweat gland response to acetylcholine (ACh) in physically trained and untrained male and female subjects.

Methods

Sweating responses were induced on the forearm and thigh in resting subjects by ACh iontophoresis using a 10% solution at 2 mA for 5 min at 26°C and 50% relative humidity.

Results

The ACh-induced sweating rate (SR) on the forearm and thigh was greater in physically trained male (P < 0.001 for the forearm and thigh, respectively) and female (P = 0.08 for the forearm, P < 0.001 for the thigh) subjects than in untrained subjects of both sexes. The SR was also significantly greater in physically trained males compared to females at both sites (P < 0.001) and in untrained males compared to females on the thigh (P < 0.02) only, although the degree of difference was greater in trained subjects than in untrained subjects. These sex differences can be attributed to the difference in sweat output per gland rather than the number of activated sweat glands.

Conclusion

We conclude that physical training enhances the ACh-induced SR in both sexes but that the degree of enhancement is greater in male than in female subjects. The effects of physical training and sex on the SR may be due to changes in peripheral sensitivity to ACh and/or sweat gland size.     

Impact of exacerbations of cystic fibrosis on muscle strength

Background

Adult patients with cystic fibrosis have peripheral muscle weakness, which is related to exercise intolerance and poor prognosis. The influence of acute exacerbations on muscle strength has been poorly studied. This study aimed to investigate whether quadriceps force (QF), as assessed with an involuntary technique, changes during intravenous antibiotics therapy (IVAT) for an exacerbation.

Methods

QF was measured in 20 patients using twitch stimulation of the femoral nerve at the day of hospitalization (day 1) and at termination (day 14) of the IVAT. Physical activity was monitored during IVAT using a SenseWear armband. Ten stable patients served as control subjects.

Results

QF did not change during exacerbation (potentiated twitch force at day 1: 140 ± 42 N, at day 14: 140 ± 47 N), but a decrease was observed in individual patients. Changes in twitch force during exacerbation were correlated with time spent in activities of at least moderate intensity (r = 0.61, p = 0.007).

Conclusions

QF does not systematically decrease during exacerbations of cystic fibrosis. Individual changes in QF are well correlated with daily time spent in activities of at least moderate intensity.     

Impaired macrophage phagocytosis of bacteria in severe asthma

Background

Bacteria are frequently cultured from sputum samples of severe asthma patients suggesting a defect in bacterial clearance from the airway. We measured the capacity of macrophages from patients with asthma to phagocytose bacteria.

Methods

Phagocytosis of fluorescently-labelled polystyrene beads, Haemophilus influenzae or Staphylococcus aureus by broncholaveolar lavage alveolar macrophages (AM) and by monocyte-derived macrophages (MDM) from non-asthmatics, mild-moderate and severe asthmatic patients was assessed using fluorimetry.

Results

There were no differences in phagocytosis of polystyrene beads by AMs or MDMs from any of the subject groups. There was reduced phagocytosis of Haemophilus influenzae and Staphylococcus aureus in MDMs from patients with severe asthma compared to non-severe asthma (p < 0.05 and p < 0.01, respectively) and healthy subjects (p < 0.01and p < 0.001, respectively). Phagocytosis of Haemophilus influenzae and Staphylococcus aureus by AM was also reduced in severe asthma compared to normal subjects (p < 0.05). Dexamethasone and formoterol did not suppress phagocytosis of bacteria by MDMs from any of the groups.

Conclusions

Persistence of bacteria in the lower airways may result partly from a reduced phagocytic capacity of macrophages for bacteria. This may contribute to increased exacerbations, airway colonization and persistence of inflammation.     

Target renal damage: the microvascular associations of increased aortic stiffness in patients with COPD

Background

Although renal impairment has been described in COPD, there is opportunity to evaluate further to determine nature and consider optimal management. Increased aortic stiffness, as seen in COPD, leads to reduced buffering of pulsatile flow. We hypothesised that urinary albumin creatinine ratio (UACR) would reflect glomerular damage related to aortic stiffness.

Methods

Patients with COPD and controls underwent spirometry, blood pressure, arterial stiffness - aortic pulse wave velocity (PWV) and provided a spot urine sample for UACR, with other renal biomarkers measured.

Results

The UACR was increased in patients (n = 52): 0.80 mg/mmol compared to controls (n = 34): 0.46 mg/mmol, p < 0.05. Aortic PWV was related to log₁₀ UACR in all subjects (r = 0.426, p < 0.001) and COPD patients alone. Aortic PWV was a significant variable for UACR with oxygen saturations, after accounting for potential confounders. Eight subjects (7 patients) reached a defined clinical microalbuminuria threshold, with aortic PWV greater in these patients compared to those patients without, although albuminuria is a continuum. Proximal tubular damage biomarkers, unlike the glomerular marker, were not different between patients and controls.

Conclusions

There is glomerular damage in patients with COPD evidenced by increased UACR, related to increased aortic stiffness. Besides the macrovascular prognostic implications of increased aortic stiffness, the microvascular state in COPD management should be considered.     

Physical activity level and its clinical correlates in chronic obstructive pulmonary disease: a cross-sectional study

Background

Decreased physical activity is associated with higher mortality in subjects with COPD. The aim of this study was to assess clinical characteristics and physical activity levels (PALs) in subjects with COPD.

Methods

Seventy-three subjects with COPD (67 ± 7 yrs, 44 female) with one-second forced expiratory volume percentage (FEV₁%) predicted values of 43 ± 16 were included. The ratio of total energy expenditure (TEE) and resting metabolic rate (RMR) was used to define the physical activity level (PAL) (PAL = TEE/RMR). TEE was assessed with an activity monitor (ActiReg), and RMR was measured by indirect calorimetry. Walking speed (measured over 30-meters), maximal quadriceps muscle strength, fat-free mass and systemic inflammation were measured as clinical characteristics. Hierarchical linear regression was applied to investigate the explanatory values of the clinical correlates to PAL.

Results

The mean PAL was 1.47 ± 0.19, and 92% of subjects were classified as physically very inactive or sedentary. The walking speed was 1.02 ± 0.23 m/s, the quadriceps strength was 31.3 ± 11.2 kg, and the fat-free mass index (FFMI) was 15.7 ± 2.3 kg/m², identifying 42% of subjects as slow walkers, 21% as muscle-weak and 49% as FFM-depleted. The regression model explained 45.5% (p < 0.001) of the variance in PAL. The FEV₁% predicted explained the largest proportion (22.5%), with further improvements in the model from walking speed (10.1%), muscle strength (7.0%) and FFMI (3.0%). Neither age, gender nor systemic inflammation contributed to the model.

Conclusions

Apart from lung function, walking speed and muscle strength are important correlates of physical activity. Further explorations of the longitudinal effects of the factors characterizing the most inactive subjects are warranted.     

Brain-derived neurotrophic factor (Val66Met) polymorphism and olfactory ability in young adults

Background

Brain- derived neurotrophic factor (BDNF) is linked to neurodegenerative diseases (e.g. Alzheimer disease and Parkinson disease) which are often characterized by olfactory impairment. A specific single nucleotide polymorphism of the BDNF gene, the Val66Met, modulates intracellular trafficking and activity-dependent secretion of BDNF protein. The aim of this study was to investigate a possible association between brain- derived neurotrophic factor Val66Met polymorphism and olfactory function, a well-known biomarker for neurodegeneration, in healthy young adults. A total of 101 subjects (45 males, age 38.7 ± 9.4 years) were assessed using the Sniffin’ Sticks Extended Test, a highly reliable commercial olfactory test composed of three sub-parts, calculating olfactory threshold (sensitivity), odor discrimination and odor identification. The Val66Met polymorphism was determined by polymerase chain reaction -restriction fragment length polymorphism (PCR-RFLP) analysis.

Results

An impaired function in Met carriers was found, especially when compared to subjects with Val/Val genotype, in the threshold (5.5 ± 2.0 vs 6.5 ± 1.8, p = 0.009), discrimination (10.3± 2.5 vs 11.9 ± 2.2, p = 0.002), and identification task (13.3 ± 1.6 vs 14.1 ± 1.3, p = 0.007), as well as in the overall TDI Score (29.1 ± 4.5 vs 32.6 ± 3.9, p < 0.001).

Conclusions

These findings appear to have implications for the evaluation of olfactory function and the relation of its impairment to cognitive decline and neurodegenerative disease.     

Associations between COPD related manifestations: a cross-sectional study

Background

Cardiovascular disease, osteoporosis and emphysema are associated with COPD. Associations between these factors and whether they predict all-cause mortality in COPD patients are not well understood. Therefore, we examined associations between markers of cardiovascular disease (coronary artery calcification [CAC], thoracic aortic calcification [TAC] and arterial stiffness), bone density (bone attenuation of the thoracic vertebrae), emphysema (PI-950 and 15th percentile) and all-cause mortality in a COPD cohort.

Methods

We assessed CAC, TAC, bone attenuation of the thoracic vertebrae, PI-950 and 15th percentile on low-dose chest computed tomography in COPD subjects. We measured arterial stiffness as carotid-radial pulse wave velocity (PWV), and identified deaths from the national register.

Results

We studied 119 COPD subjects; aged 67.8 ±7.3, 66% were males and mean FEV₁% predicted was 46.0 ±17.5. Subjects were classified into three pre-specificed groups: CAC = 0 (n = 14), 0 < CAC ≤ 400 (n = 41) and CAC > 400 (n = 64). Subjects with higher CAC were more likely to be older (p < 0.001) and male (p = 0.03), and more likely to have higher systolic blood pressure (p = 0.001) and a history of hypertension (p = 0.002) or ischemic heart disease (p = 0.003). Higher CAC was associated with higher PWV (OR 1.62, p = 0.04) and lower bone attenuation (OR 0.32, p = 0.02), but not with 15th percentile, after adjustment for age, sex and pack-years of smoking. In a Cox proportional hazards model, CAC, TAC and 15th percentile predicted all-cause mortality (HR 2.01, 2.09 and 0.66, respectively).

Conclusions

Increased CAC was associated with increased arterial stiffness and lower bone density in a COPD cohort. In addition, CAC, TAC and extent of emphysema predicted all-cause mortality.

Trial registration

Lothian NHS Board, Lothian Research Ethics Committee, LREC/2003/8/28.     

Airway wall thickness is increased in COPD patients with bronchodilator responsiveness

Rationale

Bronchodilator responsiveness (BDR) is a common but variable phenomenon in COPD. The CT characteristics of airway dimensions that differentiate COPD subjects with BDR from those without BDR have not been well described. We aimed to assess airway dimensions in COPD subjects with and without BDR.

Methods

We analyzed subjects with GOLD 1–4 disease in the COPDGene® study who had CT airway analysis. We divided patients into two groups: BDR + (post bronchodilator ΔFEV₁ ≥ 10%) and BDR-(post bronchodilator ΔFEV₁ < 10%). The mean wall area percent (WA%) of six segmental bronchi in each subject was quantified using VIDA. Using 3D SLICER, airway wall thickness was also expressed as the square root wall area of an airway of 10 mm (Pi10) and 15 mm (Pi15) diameter. %Emphysema and %gas trapping were also calculated.

Results

2355 subjects in the BDR-group and 1306 in the BDR + group formed our analysis. The BDR + group had a greater Pi10, Pi15, and mean segmental WA% compared to the BDR-group. In multivariate logistic regression using gender, race, current smoking, history of asthma, %emphysema, %gas trapping, %predicted FEV₁, and %predicted FVC, airway wall measures remained independent predictors of BDR. Using a threshold change in FEV₁ ≥ 15% and FEV₁ ≥ 12% and 200 mL to divide patients into groups, the results were similar.

Conclusion

BDR in COPD is independently associated with CT evidence of airway pathology. This study provides us with greater evidence of changes in lung structure that correlate with physiologic manifestations of airflow obstruction in COPD.     

DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease

Background

Chronic obstructive pulmonary disease (COPD) is characterized by expiratory flow limitation, causing air trapping and lung hyperinflation. Hyperinflation leads to reduced exercise tolerance and poor quality of life in COPD patients. Total lung capacity (TLC) is an indicator of hyperinflation particularly in subjects with moderate-to-severe airflow obstruction. The aim of our study was to identify genetic variants associated with TLC in COPD.

Methods

We performed genome-wide association studies (GWASs) in white subjects from three cohorts: the COPDGene Study; the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); and GenKOLS (Bergen, Norway). All subjects were current or ex-smokers with at least moderate airflow obstruction, defined by a ratio of forced expiratory volume in 1 second to forced vital capacity (FEV₁/FVC) <0.7 and FEV₁ < 80% predicted on post-bronchodilator spirometry. TLC was calculated by using volumetric computed tomography scans at full inspiration (TLC_CT). Genotyping in each cohort was completed, with statistical imputation of additional markers. To find genetic variants associated with TLC_CT, linear regression models were used, with adjustment for age, sex, pack-years of smoking, height, and principal components for genetic ancestry. Results were summarized using fixed-effect meta-analysis.

Results

Analysis of a total of 4,543 COPD subjects identified one genome-wide significant locus on chromosome 5p15.2 (rs114929486, β = 0.42L, P = 4.66 × 10⁻⁸).

Conclusions

In COPD, TLC_CT was associated with a SNP in dynein, axonemal, heavy chain 5 (DNAH5), a gene in which genetic variants can cause primary ciliary dyskinesia. DNAH5 could have an effect on hyperinflation in COPD.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-014-0097-y) contains supplementary material, which is available to authorized users.     

Mitochondrial DNA alteration in obstructive sleep apnea

Background

Obstructive Sleep Apnea (OSAS) is a disease associated with the increase of cardiovascular risk and it is characterized by repeated episodes of Intermittent Hypoxia (IH) which inducing oxidative stress and systemic inflammation. Mitochondria are cell organelles involved in the respiratory that have their own DNA (MtDNA). The aim of this study was to investigate if the increase of oxidative stress in OSAS patients can induce also MtDNA alterations.

Methods

46 OSAS patients (age 59.27 ± 11.38; BMI 30.84 ± 3.64; AHI 36.63 ± 24.18) were compared with 36 control subjects (age 54.42 ± 6.63; BMI 29.06 ± 4.7; AHI 3.8 ± 1.10). In blood cells Content of MtDNA and nuclear DNA (nDNA) was measured in OSAS patients by Real Time PCR. The ratio between MtDNA/nDNA was then calculated. Presence of oxidative stress was evaluated by levels of Reactive Oxygen Metabolites (ROMs), measured by diacron reactive oxygen metabolite test (d-ROM test).

Results

MtDNA/nDNA was higher in patients with OSAS than in the control group (150.94 ± 49.14 vs 128.96 ± 45.8; p = 0.04), the levels of ROMs were also higher in OSAS subjects (329.71 ± 70.17 vs 226 ± 36.76; p = 0.04) and they were positively correlated with MtDNA/nDNA (R = 0.5, p < 0.01).

Conclusions

In OSAS patients there is a Mitochondrial DNA damage induced by the increase of oxidative stress. Intermittent hypoxia seems to be the main mechanism which leads to this process.     

Defective alterations in the collagen network to prostacyclin in COPD lung fibroblasts

Background

Prostacyclin analogs are potent vasodilators and possess anti-inflammatory properties. However, the effect of prostacyclin on extracellular matrix (ECM) in COPD is not well known. Collagen fibrils and proteoglycans are essential ECM components in the lung and fibroblasts are key players in regulating the homeostasis of ECM proteins. The aim was to study the synthesis of prostacyclin and its effect on fibroblast activity and ECM production, and in particular collagen I and the collagen-associated proteoglycans biglycan and decorin.

Methods

Parenchymal lung fibroblasts were isolated from lungs from COPD patients (GOLD stage IV) and from lungs and transbronchial biopsies from control subjects. The prostacyclin analog iloprost was used to study the effect of prostacyclin on ECM protein synthesis, migration, proliferation and contractile capacity of fibroblasts.

Results

TGF-β₁ stimulation significantly increased prostacyclin synthesis in fibroblasts from COPD patients (p < 0.01), but showed no effect on fibroblasts from control subjects. Collagen I synthesis was decreased by iloprost in both control and COPD fibroblasts (p < 0.05). Conversely, iloprost significantly altered biglycan and decorin synthesis in control fibroblasts, but iloprost displayed no effect on these proteoglycans in COPD fibroblasts. Proliferation rate was reduced (p < 0.05) and contractile capacity was increased in COPD fibroblasts (p < 0.05) compared to control fibroblasts. Iloprost decreased proliferative rate in control fibroblasts (p < 0.05), whereas iloprost attenuated contraction capacity in both COPD (p < 0.01) and control fibroblasts (p < 0.05).

Conclusions

Iloprost reduced collagen I synthesis and fibroblast contractility but did not affect the collagen-associated proteoglycans or proliferation rate in fibroblasts from COPD patients. Enhanced prostacyclin production could lead to improper collagen network fibrillogenesis and a more emphysematous lung structure in severe COPD patients.     

Epidemiology,genetics, and subtyping of preserved ratio impaired spirometry (PRISm) in COPDGene

Background

Preserved Ratio Impaired Spirometry (PRISm), defined as a reduced FEV₁ in the setting of a preserved FEV₁/FVC ratio, is highly prevalent and is associated with increased respiratory symptoms, systemic inflammation, and mortality. Studies investigating quantitative chest tomographic features, genetic associations, and subtypes in PRISm subjects have not been reported.

Methods

Data from current and former smokers enrolled in COPDGene (n = 10,192), an observational, cross-sectional study which recruited subjects aged 45–80 with ≥10 pack years of smoking, were analyzed. To identify epidemiological and radiographic predictors of PRISm, we performed univariate and multivariate analyses comparing PRISm subjects both to control subjects with normal spirometry and to subjects with COPD. To investigate common genetic predictors of PRISm, we performed a genome-wide association study (GWAS). To explore potential subgroups within PRISm, we performed unsupervised k-means clustering.

Results

The prevalence of PRISm in COPDGene is 12.3%. Increased dyspnea, reduced 6-minute walk distance, increased percent emphysema and decreased total lung capacity, as well as increased segmental bronchial wall area percentage were significant predictors (p-value <0.05) of PRISm status when compared to control subjects in multivariate models. Although no common genetic variants were identified on GWAS testing, a significant association with Klinefelter’s syndrome (47XXY) was observed (p-value < 0.001). Subgroups identified through k-means clustering include a putative “COPD-subtype”, “Restrictive-subtype”, and a highly symptomatic “Metabolic-subtype”.

Conclusions

PRISm subjects are clinically and genetically heterogeneous. Future investigations into the pathophysiological mechanisms behind and potential treatment options for subgroups within PRISm are warranted.

Trial registration

Clinicaltrials.gov Identifier: NCT000608764.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-014-0089-y) contains supplementary material, which is available to authorized users.     

Inhibition of LPS-induced airway neutrophilic inflammation in healthy volunteers with an oral CXCR2 antagonist

Background

Inhaled lipopolysaccharide (LPS) induces a dose-dependent, acute neutrophilic response in the airways of healthy volunteers that can be quantified in induced sputum. Chemokines, such as CXCL1 and CXCL8, play an important role in neutrophilic inflammation in the lung through the activation of CXCR2 and small molecule antagonists of these receptors have now been developed. We investigated the effect of AZD8309, a CXCR2 antagonist, compared with placebo on LPS-induced inflammation measured in sputum of healthy volunteers.

Methods

Twenty healthy subjects were randomized in a double-blind placebo-controlled, cross-over study. AZD8309 (300 mg) or placebo was dosed twice daily orally for 3 days prior to challenge with inhaled LPS and induced sputum was collected 6 h later.

Results

Treatment with AZD8309 showed a mean 77% reduction in total sputum cells (p < 0.001) and 79% reduction in sputum neutrophils (p < 0.05) compared with placebo after LPS challenge. There was also a reduction in neutrophil elastase activity (p < 0.05) and CXCL1 (p < 0.05) and trends for reductions in sputum macrophages (47%), leukotriene B₄ (39%) and CXCL8 (52%).

Conclusions

AZD8309 inhibited LPS-induced inflammation measured in induced sputum of normal volunteers, indicating that this treatment may be useful in the treatment of neutrophilic diseases of the airways, such as COPD, severe asthma and cystic fibrosis.

Trial registration

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