Role of iBALT in Respiratory Immunity.

Pulmonary respiration inevitably exposes the mucosal surface of the lung to potentially noxious stimuli, including pathogens, allergens, and particulates, each of which can trigger pulmonary damage and inflammation. As inflammation resolves, B and T lymphocytes often aggregate around large bronchi to form inducible Bronchus-Associated Lymphoid Tissue (iBALT). iBALT formation can be initiated by a diverse array of molecular pathways that converge on the activation and differentiation of chemokine-expressing stromal cells that serve as the scaffolding for iBALT and facilitate the recruitment, retention, and organization of leukocytes. Like conventional lymphoid organs, iBALT recruits naïve lymphocytes from the blood, exposes them to local antigens, in this case from the airways, and supports their activation and differentiation into effector cells. The activity of iBALT is demonstrably beneficial for the clearance of respiratory pathogens; however, it is less clear whether it dampens or exacerbates inflammatory responses to non-infectious agents. Here, we review the evidence regarding the role of iBALT in pulmonary immunity and propose that the final outcome depends on the context of the disease.

Anti-Semaphorin 4D Rescues Motor, Cognitive, and Respiratory Phenotypes in a Rett Syndrome Mouse Model.

Rett syndrome is a neurodevelopmental disorder caused by mutations of the methyl-CpG binding protein 2 gene. Abnormal physiological functions of glial cells contribute to pathogenesis of Rett syndrome. Semaphorin 4D (SEMA4D) regulates processes central to neuroinflammation and neurodegeneration including cytoskeletal structures required for process extension, communication, and migration of glial cells. Blocking SEMA4D-induced gliosis may preserve normal glial and neuronal function and rescue neurological dysfunction in Rett syndrome. We evaluated the pre-clinical therapeutic efficacy of an anti-SEMA4D monoclonal antibody in the Rett syndrome Mecp2T158A transgenic mouse model and investigated the contribution of glial cells as a proposed mechanism of action in treated mice and in primary glial cultures isolated from Mecp2T158A/y mutant mice. SEMA4D is upregulated in neurons while glial fibrillary acidic protein and ionized calcium binding adaptor molecule 1-positive cells are upregulated in Mecp2T158A/y mice. Anti-SEMA4D treatment ameliorates Rett syndrome-specific symptoms and improves behavioural functions in both pre-symptomatic and symptomatic cohorts of hemizygous Mecp2T158A/y male mice. Anti-SEMA4D also reduces astrocyte and microglia activation in vivo. In vitro experiments demonstrate an abnormal cytoskeletal structure in mutant astrocytes in the presence of SEMA4D, while anti-SEMA4D antibody treatment blocks SEMA4D-Plexin B1 signaling and mitigates these abnormalities. These results suggest that anti-SEMA4D immunotherapy may be an effective treatment option to alleviate symptoms and improve cognitive and motor function in Rett syndrome.

Sex- and Region-Specific Differences in the Transcriptomes of Rat Microglia from the Brainstem and Cervical Spinal Cord.

The neural control system underlying breathing is sexually dimorphic with males being more vulnerable to dysfunction. Microglia also display sex differences, and their role in the architecture of brainstem respiratory rhythm circuitry and modulation of cervical spinal cord respiratory plasticity is becoming better appreciated. To further understand the molecular underpinnings of these sex differences, we performed RNA sequencing of immunomagnetically isolated microglia from brainstem and cervical spinal cord of adult male and female rats. We used various bioinformatics tools (Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Reactome, STRING, MAGICTRICKS) to functionally categorize identified gene sets, as well as to pinpoint common transcriptional gene drivers that may be responsible for the observed transcriptomic differences. We found few sex differences in the microglial transcriptomes derived from the brainstem, but several hundred genes were differentially expressed by sex in cervical spinal microglia. Comparing brainstem and spinal microglia within and between sexes, we found that the major factor guiding transcriptomic differences was central nervous system (CNS) location rather than sex. We further identified key transcriptional drivers that may be responsible for the transcriptomic differences observed between sexes and CNS regions; enhancer of zeste homolog 2 emerged as the predominant driver of the differentially downregulated genes. We suggest that functional gene alterations identified in metabolism, transcription, and intercellular communication underlie critical microglial heterogeneity and sex differences in CNS regions that contribute to respiratory disorders categorized by dysfunction in neural control. These data will also serve as an important resource data base to advance our understanding of innate immune cell contributions to sex differences and the field of respiratory neural control. SIGNIFICANCE STATEMENT: The contributions of central nervous system (CNS) innate immune cells to sexually dimorphic differences in the neural circuitry controlling breathing are poorly understood. We identify key transcriptomic differences, and their transcriptional drivers, in microglia derived from the brainstem and the C3-C6 cervical spinal cord of healthy adult male and female rats. Gene alterations identified in metabolism, gene transcription, and intercellular communication likely underlie critical microglial heterogeneity and sex differences in these key CNS regions that contribute to the neural control of breathing.

Lethal avian influenza A (H5N1) virus induces ataxic breathing in mice with apoptosis of pre-Botzinger complex neurons expressing neurokinin-1 receptor.

Lethal influenza A (H5N1) induces respiratory failure in humans. Although it also causes death at 7 days postinfection (dpi) in mice, the development of the respiratory failure and the viral impact on pre-Botzinger complex (PBC) neurons expressing neurokinin 1 receptor (NK1R), which is the respiratory rhythm generator, have not been explored. Body temperature, weight, ventilation, and arterial blood pH and gases were measured at 0, 2, 4, and 6 dpi in control, lethal HK483, and nonlethal HK486 viral-infected mice. Immunoreactivities (IR) of PBC NK1R, H5N1 viral nucleoprotein (NP), and active caspase-3 (CASP3; a marker for apoptosis) were detected at 6 dpi. HK483, but not HK486, mice showed the following abnormalities: 1) gradual body weight loss and hypothermia; 2) tachypnea at 2-4 dpi and ataxic breathing with long-lasting apneas and hypercapnic hypoxemia at 6 dpi; and 3) viral replication in PBC NK1R neurons with NK1R-IR reduced by 75% and CASP3-IR colabeled at 6 dpi. Lethal H5N1 viral infection causes tachypnea at the early stage and ataxic breathing and apneas (hypercapnic hypoxemia) leading to death at the late stage. Its replication in the PBC induces apoptosis of local NK1R neurons, contributing to ataxic breathing and respiratory failure.

Rejuvenating cellular respiration for optimizing respiratory function: targeting mitochondria.

Altered bioenergetics with increased mitochondrial reactive oxygen species production and degradation of epithelial function are key aspects of pathogenesis in asthma and chronic obstructive pulmonary disease (COPD). This motif is not unique to obstructive airway disease, reported in related airway diseases such as bronchopulmonary dysplasia and parenchymal diseases such as pulmonary fibrosis. Similarly, mitochondrial dysfunction in vascular endothelium or skeletal muscles contributes to the development of pulmonary hypertension and systemic manifestations of lung disease. In experimental models of COPD or asthma, the use of mitochondria-targeted antioxidants, such as MitoQ, has substantially improved mitochondrial health and restored respiratory function. Modulation of noncoding RNA or protein regulators of mitochondrial biogenesis, dynamics, or degradation has been found to be effective in models of fibrosis, emphysema, asthma, and pulmonary hypertension. Transfer of healthy mitochondria to epithelial cells has been associated with remarkable therapeutic efficacy in models of acute lung injury and asthma. Together, these form a 3R model--repair, reprogramming, and replacement--for mitochondria-targeted therapies in lung disease. This review highlights the key role of mitochondrial function in lung health and disease, with a focus on asthma and COPD, and provides an overview of mitochondria-targeted strategies for rejuvenating cellular respiration and optimizing respiratory function in lung diseases.

TNF and IL-1ß exposure increases airway narrowing but does not alter the bronchodilatory response to deep inspiration in airway segments.

BACKGROUND AND OBJECTIVE: While chronic inflammation of the airway wall and the failure of deep inspiration (DI) to produce bronchodilation are both common to asthma, whether pro-inflammatory cytokines modulate the airway smooth muscle response to strain during DI is unknown. The primary aim of the study was to determine how an inflammatory environment (simulated by the use of pro-inflammatory cytokines) alters the bronchodilatory response to DI. METHODS: We used whole porcine bronchial segments in vitro that were cultured in medium containing tumour necrosis factor and interleukin-1ß for 2 days. A custom-built servo-controlled syringe pump and pressure transducer was used to measure airway narrowing and to simulate tidal breathing with intermittent DI manoeuvres. RESULTS: Culture with tumour necrosis factor and interleukin-1ß increased airway narrowing to acetylcholine but did not affect the bronchodilatory response to DI. CONCLUSION: The failure of DI to produce bronchodilation in patients with asthma may not necessarily involve a direct effect of pro-inflammatory cytokines on airway tissue. A relationship between inflammation and airway hyper-responsiveness is supported, however, regulated by separate disease processes than those which attenuate or abolish the bronchodilatory response to DI in patients with asthma.

Wooden hutch space allowance influences male Holstein calf health, performance, daily lying time, and respiratory immunity.

Dairy calves in the western United States are commonly raised individually in wooden hutches with a space allowance of 1.23m(2)/calf. Recent legislative initiatives in California and across the United States were passed regarding concern over space allowance for farm animals. The objective of this study was to determine if rearing male Holstein calves in wooden hutches modified to increase space allowance would influence measures of performance, lying time per day, health, and respiratory immunocompetence. At 4d of age, 60 calves were randomly assigned to 1 of 3housing treatments: (1) conventional housing (CONV; 1.23m(2)/calf), (2) 1.5 × CONV (MOD; 1.85m(2)/calf), or (3) 3 × CONV (MAX; 3.71m(2)/calf). Intakes of milk and solid feed were recorded daily and body weight was measured at 0, 3, 6, 10, and 12 wk of age. For the first 3 wk of the trial, calves were scored daily for fecal consistency, hydration, and hide cleanliness. In addition, calves were scored for respiratory health (i.e., nasal and eye discharge, ear position) until 7 wk of age. The total lying duration per day was recorded using data loggers at 3, 6, and 10 wk of age. Eight clinically healthy calves from each treatment were sensitized with subcutaneous ovalbumin (OVA) and then challenged with aerosolized OVA to assess calf respiratory immunity at 11 wk of age. Bronchoalveolar lavage fluid (BALF) was collected 4d after the OVA challenge and analyzed for leukocyte differentials and OVA-specific IgG, IgG1, IgA, and IgE. Calf average daily gain and body weight were positively associated with space allowance at approximately 3 wk before weaning and throughout postweaning, respectively. A greater space allowance decreased lying time after 46d. Space allowance did not influence fecal consistency, but there was a tendency for MAX calves to take 1d longer to recover from loose feces than MOD calves. The MAX calves had the fewest (%) observations with feces on their body compared with CONV or MOD. At 3 wk of age, peripheral eosinophil concentrations decreased with increased space allowance. However, observations (%) of eye discharge increased with greater space allowance. Among calves challenged with OVA, MOD calves had the least BALF OVA-IgE, and the percent of BALF eosinophils decreased with increased space allowance. Increased space allowance for calves raised in wooden hutches may improve some measures of calf performance, health, and respiratory immunocompetence.

Dynamics of the locomotor-respiratory coupling at different frequencies.

The locomotor-respiratory coupling (LRC) is a universal phenomenon reported for various forms of rhythmic exercise. In this study, we investigated the effect of movement and respiratory frequencies on LRC. Participants were instructed to cycle or breath in synchrony with a periodic auditory stimulation at preferred and non-preferred frequencies. LRC stability was assessed by frequency and phase coupling indexes using the theory of nonlinear coupled oscillators through the sine circle map model, and the Farey tree. Results showed a stabilizing effect of sound on LRC for all frequencies and for the two systems paced. The sound-induced effect was more prominent when the rhythm of the stimulation corresponded to the preferred frequencies. The adoption of cycling or respiratory frequencies far off preferential ones led to a loss of stability in LRC. Contrary to previous findings, our results suggest that LRC is not unidirectional-from locomotion onto respiration-but bidirectional between the two systems. They also suggest that auditory information plays an important role in the modulation of LRC.

Genome-wide association study of lung function phenotypes in a founder population.

BACKGROUND: Lung function is a long-term predictor of mortality and morbidity. OBJECTIVE: We sought to identify single nucleotide polymorphisms (SNPs) associated with lung function. METHODS: We performed a genome-wide association study (GWAS) of FEV1, forced vital capacity (FVC), and FEV1/FVC in 1144 Hutterites aged 6 to 89 years, who are members of a founder population of European descent. We performed least absolute shrinkage and selection operation regression to select the minimum set of SNPs that best predict FEV1/FVC in the Hutterites and used the GRAIL algorithm to mine the Gene Ontology database for evidence of functional connections between genes near the predictive SNPs. RESULTS: Our GWAS identified significant associations between FEV1/FVC and SNPs at the THSD4-UACA-TLE3 locus on chromosome 15q23 (P = 5.7 × 10(-8) to 3.4 × 10(-9)). Nine SNPs at or near 4 additional loci had P < 10(-5) with FEV1/FVC. Only 2 SNPs were found with P < 10(-5) for FEV1 or FVC. We found nominal levels of significance with SNPs at 9 of the 27 previously reported loci associated with lung function measures. Among a predictive set of 80 SNPs, 6 loci were identified that had a significant degree of functional connectivity (GRAIL P < .05), including 3 clusters of ß-defensin genes, 2 chemokine genes (CCL18 and CXCL12), and TNFRSF13B. CONCLUSION: This study identifies genome-wide significant associations and replicates results of previous GWASs. Multimarker modeling implicated for the first time common variation in genes involved in antimicrobial immunity in airway mucosa that influences lung function.

Associations between inflammatory and immune response genes and adverse respiratory outcomes following exposure to outdoor air pollution: a HuGE systematic review.

Variants of inflammatory and immune response genes have been associated with adverse respiratory outcomes following exposure to air pollution. However, the genes involved and their associations are not well characterized, and there has been no systematic review. Thus, we conducted a review following the guidelines of the Human Genome Epidemiology Network. Six observational studies and 2 intervention studies with 14,903 participants were included (2001-2010). Six studies showed at least 1 significant gene-pollutant interaction. Meta-analysis was not possible due to variations in genes, pollutants, exposure estimates, and reported outcomes. The most commonly studied genes were tumor necrosis factor α (TNFA) (n = 6) and toll-like receptor 4 (TLR4) (n = 3). TNFA -308G>A modified the action of ozone and nitrogen dioxide on lung function, asthma risk, and symptoms; however, the direction of association varied between studies. The TLR4 single-nucleotide polymorphisms rs1927911, rs10759931, and rs6478317 modified the association of particulate matter and nitrogen dioxide with asthma. The transforming growth factor ß1 (TGFB1) polymorphism -509C>T also modified the association of pollutants with asthma. This review indicates that genes controlling innate immune recognition of foreign material (TLR4) and the subsequent inflammatory response (TGFB1, TLR4) modify the associations of exposure to air pollution with respiratory function. The associations observed have biological plausibility; however, larger studies with improved reporting are needed to confirm these findings.

Associations between respiratory sinus arrhythmia reactivity and internalizing and externalizing symptoms are emotion specific.

Internalizing and externalizing disorders are often, though inconsistently in studies of young children, associated with low baseline levels of respiratory sinus arrhythmia (RSA). RSA is thus considered to reflect the capacity for flexible and regulated affective reactivity and a general propensity for psychopathology. However, studies assessing RSA reactivity to emotional challenges tend to report more consistent associations with internalizing than with externalizing disorders, although it is unclear whether this is a function of the type of emotion challenges used. In the present study, we examined whether baseline RSA was associated with internalizing and/or externalizing severity in a sample of 273 young children (ages 5-6) with elevated symptoms of psychopathology. Following motivation-based models of emotion, we also tested whether RSA reactivity during withdrawal-based (fear, sadness) and approach-based (happiness, anger) emotion inductions was differentially associated with internalizing and externalizing symptoms, respectively. Baseline RSA was not associated with externalizing or internalizing symptom severity. However, RSA reactivity to specific emotional challenges was associated differentially with each symptom domain. As expected, internalizing symptom severity was associated with greater RSA withdrawal (increased arousal) during fearful and sad film segments. Conversely, externalizing symptom severity was related to blunted RSA withdrawal during a happy film segment. The use of theoretically derived stimuli may be important in characterizing the nature of the deficits in emotion processing that differentiate the internalizing and externalizing domains of psychopathology.

Ectosymbionts and immunity in the leaf-cutting ant Acromyrmex subterraneus subterraneus.

Associations with symbiotic organisms can serve as a strategy for social insects to resist pathogens. Antibiotics produced by attine ectosymbionts (Actinobacteria) suppress the growth of Escovopsis spp., the specialized parasite of attine fungus gardens. Our objective was to evaluate whether the presence or absence of symbiotic actinobacteria covering the whole ant cuticle is related to differential immunocompetence, respiratory rate and cuticular hydrocarbons (CHs). We evaluated these parameters in three worker groups of Acromyrmex subterraneus subterraneus: External workers (EXT), internal workers with actinobacteria covering the whole body (INB) and internal workers without actinobacteria covering the whole body (INØ). We also eliminated the actinobacteria by antibiotic treatment and examined worker encapsulation response. INB ants showed lower rates of encapsulation and respiration than did the EXT and INØ ants. The lower encapsulation rate did not seem to be a cost imposed by actinomycetes because the elimination of the actinomycetes did not increase the encapsulation rate. Instead, we propose that actinobacteria confer protection to young workers until the maturation of their immune system. Actinobacteria do not seem to change nestmate recognition in these colonies. Although it is known that actinobacteria have a specific action against Escovopsis spp., our studies, along with other independent studies, indicate that actinomycetes may also be important for the individual health of the workers.

Temporal changes in innate immune signals in a rat model of alcohol withdrawal in emotional and cardiorespiratory homeostatic nuclei.

BACKGROUND: Chronic alcohol use changes the brain's inflammatory state. However, there is little work examining the progression of the cytokine response during alcohol withdrawal, a period of profound autonomic and emotional upset. This study examines the inflammatory response in the central nucleus of the amygdala (CeA) and dorsal vagal complex (DVC), brain regions neuroanatomically associated with affective and cardiorespiratory regulation in an in vivo rat model of withdrawal following a single chronic exposure. METHODS: For qRT-PCR studies, we measured the expression of TNF-α, NOS-2, Ccl2 (MCP-1), MHC II invariant chain CD74, and the TNF receptor Tnfrsf1a in CeA and DVC samples from adult male rats exposed to a liquid alcohol diet for thirty-five days and in similarly treated animals at four hours and forty-eight hours following alcohol withdrawal. ANOVA was used to identify statistically significant treatment effects. Immunohistochemistry (IHC) and confocal microscopy were performed in a second set of animals during chronic alcohol exposure and subsequent 48-hour withdrawal. RESULTS: Following a chronic alcohol exposure, withdrawal resulted in a statistically significant increase in the expression of mRNAs specific for innate immune markers Ccl2, TNF-α, NOS-2, Tnfrsf1a, and CD74. This response was present in both the CeA and DVC and most prominent at 48 hours. Confocal IHC of samples taken 48 hours into withdrawal demonstrate the presence of TNF-α staining surrounding cells expressing the neural marker NeuN and endothelial cells colabeled with ICAM-1 (CD54) and RECA-1, markers associated with an inflammatory response. Again, findings were consistent in both brain regions. CONCLUSIONS: This study demonstrates the rapid induction of Ccl2, TNF-α, NOS-2, Tnfrsf1a and CD74 expression during alcohol withdrawal in both the CeA and DVC. IHC dual labeling showed an increase in TNF-α surrounding neurons and ICAM-1 on vascular endothelial cells 48 hours into withdrawal, confirming the inflammatory response at the protein level. These findings suggest that an abrupt cessation of alcohol intake leads to an acute central nervous system (CNS) inflammatory response in these regions that regulate autonomic and emotional state.

[Cytokines and resistive breathing].

This review summarizes and analyzes the results of the present experimental studies indicating immune system involvement in control of breathing. The hypothesis about the role of cytokines in the mechanisms of respiratory muscle fatigue and reduced ventilatory sensitivity to hypercapnia during respiration with the added resistive loading is justified. The possible ways of implementing of respiratory cytokine effects are discussed.

ILC3s control airway inflammation by limiting T cell responses to allergens and microbes.

Group 3 innate lymphoid cells (ILC3s) critically regulate host-microbe interactions in the gastrointestinal tract, but their role in the airway remains poorly understood. Here, we demonstrate that lymphoid-tissue-inducer (LTi)-like ILC3s are enriched in the lung-draining lymph nodes of healthy mice and humans. These ILC3s abundantly express major histocompatibility complex class II (MHC class II) and functionally restrict the expansion of allergen-specific CD4+ T cells upon experimental airway challenge. In a mouse model of house-dust-mite-induced allergic airway inflammation, MHC class II+ ILC3s limit T helper type 2 (Th2) cell responses, eosinophilia, and airway hyperresponsiveness. Furthermore, MHC class II+ ILC3s limit a concomitant Th17 cell response and airway neutrophilia. This exacerbated Th17 cell response requires exposure of the lung to microbial stimuli, which can be found associated with house dust mites. These findings demonstrate a critical role for antigen-presenting ILC3s in orchestrating immune tolerance in the airway by restricting pro-inflammatory T cell responses to both allergens and microbes.

Method to Obtain Pattern of Breathing in Senescent Mice through Unrestrained Barometric Plethysmography.

Unrestrained barometric plethysmography (UBP) is a method for quantifying the pattern of breathing in mice, where breathing frequency, tidal volume, and minute ventilation are routinely reported. Moreover, information can be collected regarding the neural output of breathing, including the existence of central apneas and augmented breaths. An important consideration for UBP is obtaining a breathing segment with a minimal impact of anxious or active behaviors, to elucidate the response to breathing challenges. Here, we present a protocol that allows for short, quiet baselines to be obtained in aged mice, comparable to waiting for longer bouts of quiet breathing. The use of shorter time segments is valuable, as some strains of mice may be increasingly excitable or anxious, and longer periods of quiet breathing may not be achieved within a reasonable timeframe. We placed 22 month-old mice in a UBP chamber and compared four 15 s quiet breathing segments between minutes 60-120 to a longer 10 min quiet breathing period that took 2-3 h to acquire. We also obtained counts of central apneas and augmented breaths prior to the quiet breathing segments, following a 30 min familiarization period. We show that 10 min of quiet breathing is comparable to using a much shorter 15 s duration. Additionally, the time leading up to these 15 s quiet breathing segments can be used to gather data regarding apneas of central origin. This protocol allows investigators to collect pattern-of-breathing data in a set amount of time and makes quiet baseline measures feasible for mice that may exhibit increased amounts of excitable behavior. The UBP methodology itself provides a useful and noninvasive way to collect pattern-of-breathing data and allows for mice to be tested over several time points.

Management of Respiratory Motion Artefacts in 18F-fluorodeoxyglucose Positron Emission Tomography using an Amplitude-Based Optimal Respiratory Gating Algorithm.

Positron emission tomography (PET) combined with X-ray computed tomography (CT) is an important molecular imaging platform that is required for accurate diagnosis and clinical staging of a variety of diseases. The advantage of PET imaging is the ability to visualize and quantify a myriad of biological processes in vivo with high sensitivity and accuracy. However, there are multiple factors that determine image quality and quantitative accuracy of PET images. One of the foremost factors influencing image quality in PET imaging of the thorax and upper abdomen is respiratory motion, resulting in respiration-induced motion blurring of anatomical structures. Correction of these artefacts is required for providing optimal image quality and quantitative accuracy of PET images. Several respiratory gating techniques have been developed, typically relying on acquisition of a respiratory signal simultaneously with PET data. Based on the respiratory signal acquired, PET data is selected for reconstruction of a motion-free image. Although these methods have been shown to effectively remove respiratory motion artefacts from PET images, the performance is dependent on the quality of the respiratory signal being acquired. In this study, the use of an amplitude-based optimal respiratory gating (ORG) algorithm is discussed. In contrast to many other respiratory gating algorithms, ORG permits the user to have control over image quality versus the amount of rejected motion in the reconstructed PET images. This is achieved by calculating an optimal amplitude range based on the acquired surrogate signal and a user-specified duty cycle (the percentage of PET data used for image reconstruction). The optimal amplitude range is defined as the smallest amplitude range still containing the amount of PET data required for image reconstruction. It was shown that ORG results in effective removal of respiration-induced image blurring in PET imaging of the thorax and upper abdomen, resulting in improved image quality and quantitative accuracy.

Time and dose-dependent impairment of neonatal respiratory motor activity after systemic inflammation.

Neonatal respiratory impairment during infection is common, yet its effects on respiratory neural circuitry are not fully understood. We hypothesized that the timing and severity of systemic inflammation is positively correlated with impairment in neonatal respiratory activity. To test this, we evaluated time- and dose-dependent impairment of in vitro fictive respiratory activity. Systemic inflammation (induced by lipopolysaccharide, LPS, 5 mg/kg, i.p.) impaired burst amplitude during the early (1 h) inflammatory response. The greatest impairment in respiratory activity (decreased amplitude, frequency, and increased rhythm disturbances) occurred during the peak (3 h) inflammatory response in brainstem-spinal cord preparations. Surprisingly, isolated medullary respiratory circuitry within rhythmic slices showed decreased baseline frequency and delayed onset of rhythm only after higher systemic inflammation (LPS 10 mg/kg) early in the inflammatory response (1 h), with no impairments at the peak inflammatory response (3 h). Thus, different components of neonatal respiratory circuitry have differential temporal and dose sensitivities to systemic inflammation, creating multiple windows of vulnerability for neonates after systemic inflammation.

Dampness in dorm rooms and its associations with allergy and airways infections among college students in China: a cross-sectional study.

UNLABELLED: A cross-sectional study was carried out at Tianjin University campus, China, from February 21 to June 10, 2006, to survey the association between dampness in dorms, and allergy and airways infections among college students. The health and dampness conditions were self-reported by 3436 students living in 1511 dorm rooms located in 13 buildings on the campus. The buildings were selected according to their positions, construction periods and occupant densities. The symptoms involved wheezing, dry cough during night, rhinitis, eczema, cold/flu, ear inflammation, pneumonia and tuberculosis. The indoor moisture signs were mould/damp spots on walls, ceilings and floors; suspected or ever happened water damage; condensation on windowpane in winter and odours perceived by subjects themselves. There was a significant positive association between condensation and dry cough. Eczema was often reported in rooms with moisture problem. Dampness was a significant risk factor for common cold. PRACTICAL IMPLICATIONS: Dampness problems in dorms of Chinese students are a risk factor for allergic symptoms, and hence there is a need for dorm environment improvement. Health problems related to ventilation and microbiology problems in dorms should be further studied.