Progression of pulmonary hyperinflation and trapped gas associated with genetic and environmental factors in children with cystic fibrosis

BACKGROUND: Functional deterioration in cystic fibrosis (CF) may be reflected by increasing bronchial obstruction and, as recently shown, by ventilation inhomogeneities. This study investigated which physiological factors (airway obstruction, ventilation inhomogeneities, pulmonary hyperinflation, development of trapped gas) best express the decline in lung function, and what role specific CFTR genotypes and different types of bronchial infection may have upon this process. METHODS: Serial annual lung function tests, performed in 152 children (77 males; 75 females) with CF (age range: 6-18 y) provided data pertaining to functional residual capacity (FRCpleth, FRCMBNW), volume of trapped gas (VTG), effective specific airway resistance (sReff), lung clearance index (LCI), and forced expiratory indices (FVC, FEV1, FEF50). RESULTS: All lung function parameters showed progression with age. Pulmonary hyperinflation (FRCpleth > 2SDS) was already present in 39% of patients at age 6-8 yrs, increasing to 67% at age 18 yrs. The proportion of patients with VTG > 2SDS increased from 15% to 54% during this period. Children with severe pulmonary hyperinflation and trapped gas at age 6-8 yrs showed the most pronounced disease progression over time. Age related tracking of lung function parameters commences early in life, and is significantly influenced by specific CFTR genotypes. The group with chronic P. aeruginosa infection demonstrated most rapid progression in all lung function parameters, whilst those with chronic S. aureus infection had the slowest rate of progression. LCI, measured as an index of ventilation inhomogeneities was the most sensitive discriminator between the 3 types of infection examined (p < 0.0001). CONCLUSION: The relationships between lung function indices, CFTR genotypes and infective organisms observed in this study suggest that measurement of other lung function parameters, in addition to spirometry alone, may provide important information about disease progression in CF.

Effects of genetic and environmental factors on chronic lower airway disease in horses

BACKGROUND: Environment and genetics influence the manifestation of recurrent airway obstruction (RAO), but the associations of specific factors with mild, moderate, and severe clinical signs are unknown. HYPOTHESIS: We hypothesized that sire, feed, bedding, time outdoors, sex, and age are associated with clinical manifestations of mild, moderate, and severe lower airway disease. ANIMALS: Direct offspring of 2 RAO-affected Warmblood stallions (F1S1, n = 172; F1S2, n = 135); maternal half-siblings of F1S1 (mHSS1, n = 66); and an age-matched, randomly chosen control group (CG, n = 33). METHODS: A standardized questionnaire was used to assess potential risk factors and to establish a horse owner assessed respiratory signs index (HOARSI 1-4, from healthy to severe) according to clinical signs of lower airway disease. RESULTS: More F1S1 and F1S2 horses showed moderate to severe clinical signs (HOARSI 3 and HOARSI 4 combined, 29.6 and 27.3%, respectively) compared with CG and mHSS1 horses (9.1 and 6.2%, respectively; contingency table overall test, P < .001). Sire, hay feeding, and age (in decreasing order of strength) were associated with more severe clinical signs (higher HOARSI), more frequent coughing, and nasal discharge. CONCLUSIONS AND CLINICAL RELEVANCE: There is a genetic predisposition and lesser but also marked effects of hay feeding and age on the manifestation of moderate to severe clinical signs, most markedly on coughing frequency. In contrast, mild clinical signs were not associated with sire or hay feeding in our populations.

Climatic and environmental changes during the Weichselian Lateglacial Interstadial in the Weerterbos region, the Netherlands

Lake sediment records from the Weerterbos region, in the southern Netherlands, were studied to reconstruct summer temperature and environmental changes during the Weichselian Lateglacial Interstadial. A sediment core obtained from a small lacustrine basin was analysed for multiple proxies, including lithological changes, oxygen isotopes of bulk carbonates, pollen and chironomids. It was found that the oxygen isotope record differed strongly from the other proxies. Based on a comparison with three additional lake sediment records from the same region, it emerged that the oxygen isotope records were strongly affected by local environmental conditions, impeding the distinction of a regional palaeoclimate signal. The chironomid-inferred July air temperature reconstruction produced inferred interstadial temperatures ranging between ∼15° and 18°C, largely consistent with previously published results from the northern part of the Netherlands. A temporary regressive phase in the pollen record, which can be tentatively correlated with the Older Dryas, preceded the expansion of birch woodland. Despite differences between the four pollen records from the Weerterbos region, a comparable regressive vegetation phase that was possibly the result of a shift to drier conditions could be discerned in all of the profiles. In addition, a temporary temperature decline of ∼1.5°C was inferred from the chironomid record during this regressive phase. The multi-proxy approach used here enabled a direct comparison of inferred changes in temperature, vegetation and environmental conditions at an individual site, while the multi-site approach provided insight into the factors influencing the pollen and isotope records from these small-scale depressions.

The role of upper-level dynamics and surface processes for the Pakistan flood of July 2010

In July and August 2010 floods of unprecedented impact afflicted Pakistan. The floods resulted from a series of intense multi-day precipitation events in July and early August. At the same time a series of blocking anticyclones dominated the upper-level flow over western Russia and breaking waves i.e. equatorward extrusions of stratospheric high potential vorticity (PV) air formed along the downstream flank of the blocks. Previous studies suggested that these extratropical upper-level breaking waves were crucial for instigating the precipitation events in Pakistan. Here a detailed analysis is provided of the extratropical forcing of the precipitation. Piecewise PV inversion is used to quantify the extratropical upper-level forcing associated with the wave breaking and trajectories are calculated to study the pathways and source regions of the moisture that precipitated over Pakistan. Limited-area model simulations are carried out to complement the Lagrangian analysis. The precipitation events over Pakistan resulted from a combination of favourable boundary conditions with strong extratropical and monsoonal forcing factors. Above-normal sea-surface temperatures in the Indian Ocean led to an elevated lower-tropospheric moisture content. Surface monsoonal depressions ensured the transport of moist air from the ocean towards northeastern Pakistan. Along this pathway the air parcel humidity increased substantially (60–90% of precipitated moisture) via evapotranspiration from the land surface. Extratropical breaking waves influenced the surface wind field substantially by enhancing the wind component directed towards the mountains which reinforced the precipitation.