The need for systematic quality controls in implementing N95 reprocessing and sterilization.

BACKGROUND: Due to increased requirement for personal protective equipment during the coronavirus disease 2019 pandemic, many medical centres utilized sterilization systems approved under Food and Drug Administration Emergency Use Authorization for single-use N95 mask re-use. However, few studies have examined the real-world clinical challenges and the role of ongoing quality control measures in successful implementation. AIMS: To demonstrate successful implementation of quality control measures in mask reprocessing, and the importance of continued quality assurance. METHODS: A prospective quality improvement study was conducted at a tertiary care medical centre. In total, 982 3M 1860 masks and Kimberly-Clark Tecnol PFR95 masks worn by healthcare workers underwent sterilization using a vaporized hydrogen peroxide gas plasma-based reprocessing system. Post-processing qualitative fit testing (QFT) was performed on 265 masks. Mannequin testing at the National Institute for Occupational Safety and Health (NIOSH) laboratory was used to evaluate the impact of repeated sterilization on mask filtration efficacy and fit. A locally designed platform evaluated the filtration efficiency of clinically used and reprocessed masks. FINDINGS: In total, 255 N95 masks underwent QFT. Of these, 240 masks underwent post-processing analysis: 205 were 3M 1860 masks and 35 were PFR95 masks. Twenty-five (12.2%) of the 3M masks and 10 (28.5%) of the PFR95 masks failed post-processing QFT. Characteristics of the failed masks included mask deformation (N=3, all 3M masks), soiled masks (N=3), weakened elastic bands (N=5, three PFR95 masks), and concern about mask shrinkage (N=3, two 3M masks). NIOSH testing demonstrated that while filter efficiency remained >98% after two cycles, mask strap elasticity decreased by 5.6% after reprocessing. CONCLUSIONS: This study demonstrated successful quality control implementation for N95 mask disinfection, and highlights the importance of real-world clinical testing beyond laboratory conditions.

Imaging Tolerance Induction in the Classic Medawar Neonatal Mouse Model: Active Roles of Multiple F1-Donor Cell Types.

The immature immune system is uniquely susceptible to tolerance induction and thus an attractive target for immunomodulation strategies for organ transplantation. Newborn mice injected with adult semi-allogeneic lymphohematopoietic cells accept transplants without immunosuppressive drugs. Early in vivo/in situ events leading to neonatal tolerance remain poorly understood. Here, we show by whole body/organ imaging that injected cells home to lymphoid organs and liver where various F1-donor cell types selectively alter neonatal immunity. In host thymus, F1-donor dendritic cells (DC) interact with developing thymocytes and regulatory T cells suggesting a role in negative selection. In spleen and lymph nodes, F1-donor regulatory T/B cells associate with host alloreactive cells and by themselves prolong cardiac allograft survival. In liver, F1-donor cells give rise to albumin-containing hepatocyte-like cells. The neonatal immune system is lymphopenic, Th-2 immunodeviated and contains immature DC, suggesting susceptibility to regulation by adult F1-donor cells. CD8a T cell inactivation greatly enhances chimerism, suggesting that variable emerging neonatal alloreactivity becomes a barrier to tolerance induction. This comprehensive qualitative imaging study systematically shows contribution of multiple in vivo processes leading simultaneously to robust tolerance. These insights into robust tolerance induction have important implications for development of strategies for clinical application.

Respiratory responses to diverse indoor combustion air pollution sources.

UNLABELLED: Diverse indoor combustion sources contribute to the indoor air environment. To evaluate the effect of these sources on human respiratory health, we examined associations between respiratory conditions and household factors in the 2360 children's fathers (mean = 38.4 years old) and associations between lung function and household factors in 463 primary school children (mean = 8.3 years old) from Wuhan, China. Factor analysis developed new uncorrelated 'factor' variables. Unconditional logistic regression models or linear regression models, controlling for important covariates, estimated the respiratory health effects. Coal smoke derived from home heating ('heating coal smoke') was associated with high adult reporting of persistent cough, persistent phlegm, and wheeze. Cooking coal smoke was associated with physician-diagnosed adult asthma and decreased forced vital capacity (FVC), and forced expiratory volume at 1 s (FEV(1)) in children. The presence of any home cigarette smoker was associated with more reports of persistent cough, persistent phlegm, cough with phlegm, and bronchitis. Our study suggests that in Wuhan, there may be independent respiratory health effects of different indoor combustion sources and their exposure factors for these study populations. PRACTICAL IMPLICATIONS: We conclude that multiple indoor air pollution sources could have adverse respiratory health effects on both children and middle-aged men in the city of Wuhan, China. These results may have implications for the Wuhan local government, the Chinese government, or other related organizations in efforts on protecting public health through regulation of indoor air pollution from indoor combustion sources.

Transbronchial biopsy with virtual CT bronchoscopy and nodal highlighting.

Transbronchial biopsy to sample lymph nodes and tumors that are not visible at endoscopy has a poor (<50%) success rate. These nodes can be highlighted easily at virtual computed tomographic (CT) bronchoscopy to provide a guide. This study was performed to evaluate if the addition of this information to the bronchoscopist improved the success rate of transbronchial biopsy of subcarinal and aortopulmonary lymph nodes. The addition of virtual CT bronchoscopy with lymph node highlighting significantly (P < .5) increased biopsy success rates for pretracheal, hilar, and high pretracheal adenopathy.

Pulmonary medicine and palliative care.

Gynaecological malignancies affect the respiratory system both directly and indirectly. Malignant pleural effusion is a poor prognostic factor: management options include repeated thoracentesis, chemical pleurodesis, symptomatic relief of dyspnoea with oxygen and morphine, and external drainage. Parenchymal metastases are typically multifocal and respond to chemotherapy, with a limited role for pulmonary metastatectomy. Pulmonary tumour embolism is frequently associated with lymphangitic carcinomatosis, and is most common in choriocarcinoma. Thromboembolic disease, associated with the hypercoagulable state of cancer, is treated with anticoagulation. Inferior vena cava filter placement is indicated when anticoagulation cannot be given, or when emboli recur despite adequate anticoagulation. Palliative care has a major role for respiratory symptoms of gynaecological malignancies. Treatable causes of dyspnoea include bronchospasm, fluid overload and retained secretions. Opiates are effective at relieving dyspnoea associated with effusions, metatases, and lymphangitic tumour spread. Non-pharmacological therapies include energy conservation, home redesign, and dyspnoea relief strategies, including pursed lip breathing, relaxation, oxygen, circulation of air with a fan, and attention to spiritual suffering. Identification and treatment of gastroesophageal reflux, sinusitis, and asthma can improve many patients' coughs. Chest wall pain responds to local radiotherapy, nerve blocks or systemic analgesia. Case examples illustrate ways to address quality of life issues.

The relationship between particle deposition in the anterior nasal passage and nasal passage characteristics.

The objective of this study was to examine the effects of nasal passage characteristics on anterior particle deposition during cyclical breathing. Forty healthy, nonsmoking, adult subjects participated in this study. Nasal passage characteristics such as nostril length, width, angle, ellipticity, and minimum nasal cross-sectional area were measured. The subjects inhaled a polydisperse radioactively tagged aerosol (mass median aerodynamic diameter = 5.4 microns, geometric standard deviation [GSD] = 1.3) into the nose and exhaled through the mouth. The amount of radioactivity in the nose was measured immediately after inhalation and thereafter for 54 minutes. At 52.5 minutes, subjects wiped the accessible portion of the anterior nose to remove any remaining activity. The difference in activity at 52 and 54 minutes was used as a measure of activity removed during the nose wipe. Percentage of activity in the nasal passage at 52 minutes and percentage of activity removed with the nose wipe were considered surrogates for particles deposited in the anterior nasal passage. A multiple regression analysis showed that the degree of ellipticity of the nostrils was significantly related to particle deposition in the anterior nasal passage. These results suggest that ellipticity of the nostrils may be a determinant of the amount of particle deposition in the anterior nasal passage.

Bacterial endotoxin is an active component of cigarette smoke.

BACKGROUND: Chronic bronchitis in cigarette smokers shares many clinical and histologic features with environmental lung diseases attributed to bacterial endotoxin (lipopolysaccharide [LPS]) inhalation. Experimental LPS inhalation mimics many of the acute effects of cigarette smoke in the lower airway. Therefore, we reasoned that LPS may be a biologically active component of cigarette smoke. DESIGN: The Limulus amebocyte lysate (LAL) assay was used to measure LPS in the tobacco and filter tip components of unsmoked 1R4F experimental cigarettes and commercially available "light" cigarettes, as well as in mainstream (MS) and sidestream (SS) smoke particles generated with an automated smoking machine and collected on ventilator mainflow filters. SETTING AND PARTICIPANTS: Blood LPS activity and plasma cytokine concentrations were measured in groups of healthy smokers and nonsmokers who reported to the walk-in clinic at the Baltimore VA Medical Center for unrelated complaints. MEASUREMENTS: Blood LPS levels were measured by LAL assay and plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), soluble TNF receptors I and II (sTNFR I and sTNFR II) were measured by enzyme-linked immunosorbent assay. RESULTS: Bioactive LPS was detected in both the tobacco portion (1R4F, 17.8+/-1.0 microg/cigarette; light, 26.8+/-7.3 microg/cigarette [mean+/-SE]) and filter tips (1R4F, 0.67+/-0.55 microg/cigarette; light, 0.70+/-0.39 microg/cigarette) of cigarettes. Bioactive LPS was also detected in both MS (1R4F, 120+/-64 ng/cigarette; light: 45.3+/-16 ng/cigarette) and SS smoke (1R4F, 18+/-1.5 ng/cigarette; light: 75+/-49 ng/cigarette). Although systemic absorption of inhaled LPS may occur, we failed to detect any differences between nonsmokers and smokers in median blood LPS levels (median values, 66.75 and 72.1 pg/mL, respectively; p = 0.55) or plasma concentrations of TNF-alpha (0 vs 0 pg/mL, respectively; p = 0.71), sTNFR I(1,469 vs 1,576 pg/mL, respectively), sTNFR II (2,011 vs 3,110 pg/mL, respectively), or IL-6 (8.8 vs 0 pg/mL, respectively; p = 0.20). CONCLUSIONS: Smoking one pack of cigarettes per day delivers a dose of respirable LPS that is comparable to the levels of LPS associated with adverse health effects in cotton textile workers. Thus, we suggest that the bioactive LPS in cigarette smoke may contribute to the pathogenesis of chronic bronchitis that develops in susceptible cigarette smokers.

Identification and characterization of golgin-84, a novel Golgi integral membrane protein with a cytoplasmic coiled-coil domain.

The cytoplasmic face of the Golgi contains a variety of proteins with coiled-coil domains. We identified one such protein in a yeast two-hybrid screen, using as bait the peripheral Golgi phosphatidylinositol(4,5)P2 5-phosphatase OCRL1 that is implicated in a human disease, the oculocerebrorenal syndrome. The approximately 2.8-kilobase mRNA is ubiquitously expressed and abundant in testis; it encodes a 731-amino acid protein with a predicted mass of 83 kDa. Antibodies against the sequence detect a novel approximately 84-kDa Golgi protein we termed golgin-84. Golgin-84 is an integral membrane protein with a single transmembrane domain close to its C terminus. In vitro, the protein inserts post-translationally into microsomal membranes with an N-cytoplasmic and C-lumen orientation. Cross-linking indicates that golgin-84 forms dimers, consistent with the prediction of an approximately 400-residue dimerizing coiled-coil domain in its N terminus. The dimerization potential is supported by a data base search that showed that the N-terminal 497 residues of golgin-84 contain a coiled-coil domain that when fused to the RET tyrosine kinase domain had the ability to activate it, forming the RET-II oncogene. Data base searching also indicates golgin-84 is similar in structure and sequence to giantin, a membrane protein that tethers coatamer complex I vesicles to the Golgi.

Acute respiratory response to prolonged, moderate levels of sidestream tobacco smoke.

Environmental tobacco smoke (ETS) is a significant component of indoor air pollution yet the acute upper respiratory response has not been well studied. The goal of this study was to determine the response of healthy subjects to moderate levels of sidestream tobacco smoke (SS). Twenty-three subjects were challenged on 2 separate days to clean air or SS (2 h, 15 ppm carbon monoxide, at rest). Subjects completed symptom questionnaires, posterior rhinomanometry, and body plethysmography. Average total and differential cell counts and albumin concentration were determined on nasal lavage samples. The urinary cotinine: creatinine ratio was used as a biomarker of exposure. Following SS exposure, irritant and rhinitis symptoms increased, nasal resistance rose from 4.9+/-0.4 to 6.3+/-0.6 cm H2O/L/s and specific airway conductance decreased from 0.14+/-0.01 to 0.13+/-0.01 cm H2O(-1) s(-1). Total cell counts, neutrophils, and albumin were unchanged. An increased nasal congestive response did not correlate with an increased cotinine: creatinine ratio. A history of ETS rhinitis did not predict an increased group response to smoke, but individuals with the largest physiologic and inflammatory response were historically ETS sensitive. In summary, healthy normal subjects demonstrate nasal congestion with exposure to moderate levels of SS without evidence of increased nasal vascular permeability.

Neurogenic inflammation: with additional discussion of central and perceptual integration of nonneurogenic inflammation.

The Working Group on Neurogenic Inflammation proposed 11 testable hypotheses in the three domains of neurogenic inflammation, perceptual and central integration, and nonneurogenic inflammation. The working group selected the term people reporting chemical sensitivity (PRCS) to identify the primary subject group. In the domain of neurogenic inflammation, testable hypotheses included: PRCS have an increased density of c-fiber neurons in symptomatic tissues; PRCS produce greater quantities of neuropeptides and prostanoids than nonsensitive subjects in response to exposure to low-level capsaicin or irritant chemicals; PRCS have an increased and prolonged response to exogenously administered c-fiber activators such as capsaicin; PRCS demonstrate augmentation of central autonomic reflexes following exposure to agents that produce c-fiber stimulation; PRCS have decreased quantities of neutral endopeptidase in their mucosa; exogenous neuropeptide challenge reproduces symptoms of PRCS. In the domain of perceptual and central integration, testable hypotheses included: PRCS have alterations in adaptation, habituation, cortical representation, perception, cognition, and hedonics compared to controls; the qualitative and quantitative interactions between trigeminal and olfactory systems are altered in PRCS; higher integration of sensory inputs is altered in PRCS. In the domain of nonneurogenic inflammation, testable hypotheses included: increased inflammation is present in PRCS in symptomatic tissues and is associated with a heightened neurosensory response; PRCS show an augmented inflammatory response to chemical exposure. The working group recommended that studies be initiated in these areas.

Glucocorticoids induce beta2-adrenergic receptor function in human nasal mucosa.

Glucocorticoids are hypothesized to induce beta2-adrenergic receptors (beta2-R) and their functions. The ability of dexamethasone (DEX) in vitro and beclomethasone dipropionate (BDP) in vivo to induce beta2-R messenger RNA (mRNA) and function was investigated in human nasal mucosa. In this tissue, albuterol does not stimulate exocytosis either in vivo or in vitro (Mullol and coworkers, 1992). Therefore, induction of beta2-R-mediated glandular exocytosis by glucocorticoids was proposed as an unambiguous outcome measure. Human nasal mucosa was cultured for 3 d with and without 1 microM DEX, then challenged with media or 100 microM albuterol. Culture supernatants were collected for measurement of exocytosed glandular products. Explant mRNA was extracted for reverse transcriptase-polymerase chain reaction (RT-PCR), and in situ hybridization of beta2-R mRNA performed. In vivo, normal subjects received saline or BDP for 3 d before albuterol nasal provocation. Concentrations of exocytosed products were measured in nasal secretions. RNA was extracted from nasal epithelial scrapings for RT-PCR. In vitro, DEX treatment induced albuterol-mediated glandular exocytosis (p < 0.04), and increased the steady-state beta2-R/beta-actin mRNA ratio (p < 0.05), and expression of beta2-R mRNA in glands. In vivo, BDP increased the beta2-R/beta-actin mRNA ratio in epithelial scrapings (p < 0.04), but did not induce albuterol-mediated glandular secretion. We conclude that glucocorticoids increase steady-state beta2-R mRNA levels in vivo and in vitro, and can induce beta2-R function as assessed by submucosal gland exocytosis in vitro. While topical BDP induced epithelial beta2-R mRNA, it did not modulate exocytosis from the deeper submucosal glands.

Differential susceptibility to inhaled pollutants: effects of demographics and diseases.

Inhaled pollutants and respiratory disease deserve particular attention at a conference focused on susceptibility and environmental risk. Inhaled air contains diverse biological, physical and chemical stressors which may cause upper and lower respiratory inflammation and exacerbate complex polygenic disorders such as asthma and sinusitis. This paper focuses on intrinsic susceptibility factors of demographics and diseases as well as genetic background. The National Health Information Survey shows that acute and chronic respiratory conditions are common at all ages, but their incidence and prevalence vary between age groups. Susceptibility is therefore not a fixed characteristic, but the aggregate effect of changing intrinsic factors such as age and disease. While ethnicity is often cited as a risk factor for disease prevalence or severity, recent research shows that measurable factors such as nasal ellipticity determine exposure-dose relationships, while the imperfect surrogate of ethnicity does not. Studies also show that exposure-dose relationships can be modified by recent exposures, and additional information is clearly needed in this area. We propose that evidence for the genetic contribution to pollutant susceptibility be sought in inter-individual variation in responses of homogenous, well characterized individuals to short term controlled pollutant exposure. Future improvements in risk assessment models will be based on a precise identification of factors that determine exposure-dose relationships, and a mechanistic understanding of the reasons that a demographic factor or disease appears to confer altered susceptibility.

Environmental factors and respiratory hypersensitivity: the Americas.

Diverse environmental exposure profiles exist in the Americas because of widely different climates, ambient pollutants, and bioaerosols in these continents. This paper reviews selected studies from the Americas that support the broad hypothesis that environmental factors contribute to respiratory hypersensitivity. Processes influenced by environmental factors include primary immunologic sensitization, the development and exacerbation of specific immunologic diseases and the activation of nonspecific mechanisms with tissue inflammation, injury and remodeling. Endpoints resulting from these processes include respiratory symptoms, diseases such as asthma, with measures of disease severity including medication use and hospitalization rates, and death due to cardiorespiratory disease. Studies associate sensitization rates to specific allergens with environmental factors such as humidity and indices of allergen exposure. Regional variation occurs with exposure to outdoor source pollutants such as ozone, but varies by household to bioaerosols such as dust mite, cat or cockroach allergen. Indoor allergens are associated with asthma while outdoor allergens are associated with allergic rhinitis. In a national survey, the atopic sensitization rate in the USA increased with urban residence (defined as towns of population > 2500) and varied by region. Controlled human challenge studies show that ozone increases the response of allergic subjects to allergen. Increased ambient photochemical pollution concentrations, of which ozone is an important component, are associated with increased emergency room visits for asthma in cities such as Toronto, New York, Atlanta, and Mexico City. In Sao Paolo, Brazil, mortality due to childhood respiratory disease was influenced by the ambient levels of NO2. Epidemiologic studies including the recent meta-analysis of a large, longitudinal study population associate ambient concentrations of particulate matter < 10 microns and respiratory symptoms, disease severity and increased cardiorespiratory deaths. Toxicology studies show that individual variation in responsiveness is important in nonspecific inflammatory responses to irritant pollutants such as ozone and environmental tobacco smoke. These studies indicate that environmental factors influence primary allergen sensitization, secondary allergic responses, the activation of nonspecific inflammatory responses, and the severity of respiratory diseases, including asthma.

Evaluation of acoustic rhinometry and posterior rhinomanometry as tools for inhalation challenge studies.

Objective measures of upper respiratory function are needed to understand the effects of inhaled toxicants on the nasal passages. Acoustic rhinometry (AR) is a simple new technique that determines nasal volume by measuring the cross-sectional area of the upper airway as a function of the distance along the nasal passage. This study compares acoustic rhinometry with the more traditional posterior rhinomanometry (NAR) and correlates these objective measures with the symptom of nasal congestion. Healthy young adults (n = 29) were studied on 4 days, each separated by at least 1 wk, in a climate-controlled environmental chamber for 6 h, with exposure to clean air or sidestream tobacco smoke (SS) (2 h, 1, 5, and 15 ppm CO). The coefficient of variation for single measurements was 8-15% (AR) and 4% (NAR); for across-day measurements it was 15-25% (AR) and 13-15% (NAR); and for between days it was 19-27% AR and 17-21% (NAR). These coefficients were similar in subjects with a history of environmental tobacco smoke sensitivity (ETS-S) and those with no history of ETS sensitivity (ETS-NS). At baseline, the perception of unilateral nasal congestion was significantly correlated with unilateral nasal dimensions or nasal resistance; the symptom of baseline bilateral nasal congestion (estimated for both nasal passages simultaneously) correlated less well with objective measures of nasal patency. Under challenge conditions (SS at 1-15 ppm CO), there were typically significant correlations between changes in unilateral congestion and both unilateral rhinomanometry and acoustic rhinometry, but correlations of bilateral congestion and measurable dimensions were much lower. ETS-S and ETS-NS subjects differed in correlations between bilateral subjective and objective measures: ETS-S subjects showed significant correlation between baseline congestion and NAR; in contrast, ETS-NS subjects showed significant correlation between baseline congestion and acoustic rhinometry. These results indicate that NAR and AR are complementary tests for use in inhalation challenge studies and have different correlations with nasal congestion under baseline and challenge conditions.

Tobacco smoke upper respiratory response relationships in healthy nonsmokers.

This study determined exposure-response relationships to side-stream tobacco smoke (2 hrs; 0, 1, 5, and 15 ppm CO) in 29 healthy nonsmoking young adults. Sixteen subjects had no history of environmental tobacco smoke rhinitis (ETS-NS) while 13 subjects had a history of ETS rhinitis (ETS-S). Eye irritation and odor perception showed a statistically significant exposure response in both groups; headache was significant in ETS-S and nose irritation was significant in ETS-NS subjects. Significant postexposure (P1) symptoms were first reported at 1 ppm CO among both groups, but in 3/9 symptoms were significantly greater at this exposure level in ETS-S subjects. Nasal congestion, rhinorrhea, and cough increased significantly at 15 ppm CO only. In ETS-S subjects, nasal volume decreased and nasal resistance increased in an exposure-response fashion. ETS-NS subjects had a qualitatively different shape to the exposure-response curve; significant dimensional reductions in mid- and posterior nasal volume occurred with exposure at 1 ppm CO but not at 5 ppm CO and reductions in posterior nasal volume occurred at 15 ppm CO exposure. These studies indicate subjective and objective response relationships with exposure to sidestream tobacco smoke at concentrations from 1 to 15 ppm CO. Some differences are noted among the two subject groups in the magnitude of some symptoms at the lowest exposure level and in the qualitative shape of the acoustic rhinometry and nasal resistance exposure-response curves.

Sidestream tobacco smoke exposure acutely alters human nasal mucociliary clearance.

Nasal mucociliary clearance (NMC) is a biomarker of nasal mucosal function. Tobacco smokers have been shown to have abnormal NMC, but the acute effect of environmental tobacco smoke (ETS) on nonsmokers is unknown. This study evaluated acute tobacco smoke-induced alterations in NMC in 12 healthy adults. Subjects were studied on 2 days, separated by at least 1 week. Subjects underwent a 60-min controlled exposure at rest to air or sidestream tobacco smoke (SS) (15 ppm CO) in a controlled environmental chamber. One hour after the exposure, 99mTc-sulfur colloid was aerosolized throughout the nasal passage and counts were measured with a scintillation detector. Six out of 12 subjects showed more rapid clearance after smoke exposure than after air exposure, and 3/12 had rapid clearance on both days. However, substantial decreases in clearance occurred in 3/12 subjects, all of whom had a history of ETS rhinitis. In two subjects, more than 90% of the tracer remained 1 hr after tracer administration (2 hr after smoke exposure). Understanding the basis for biologic variability in the acute effect of tobacco smoke on NMC may advance our understanding of pathogenesis of chronic effects of ETS.

Mutation analysis of the ROM1 gene in retinitis pigmentosa.

To examine the role of ROM1, a homologue of peripherin/RDS, in autosomal dominant retinitis pigmentosa (adRP), we screened 224 adRP and 29 simplex RP probands for ROM1 mutations. Four ROM1 alleles were designated as potentially pathogenic because they were found only in RP patients but not in 50-100 controls nor in 249 other RP probands. The substitutions P60T and T108M were present in a single allele in a subject with typical adRP, and this allele cosegregated with the disease in the small family. The putative null allele L114 [1 bp] was present in an individual with atypical RP but not in three unaffected siblings. This insertion has been previously reported to cause RP only when accompanied by a peripherin/RDS mutation, but no peripherin/RDS mutations were found in any of the four probands reported here. Two substitutions (G75D, R242Q) were present in two other probands with simplex RP. These data suggest that potentially pathogenic ROM1 mutations occur in 1% or less of patients with adRP or simplex RP. The absence of detectable peripherin/RDS mutations in these families suggests either that: (i) mutations in other digenic partners are required for pathogenic ROM1 alleles to cause retinal degeneration; (ii) these ROM1 mutations do not cause RP; or (iii) peripherin/RDS mutations are present but were not identified in these patients.

Nasal pressure-volume relationships determined with acoustic rhinometry.

Partitioning of ventilation has been hypothesized to be related to nasal pressure-volume relationships, relationships that have been difficult to measure. Regional differences in nasal passage pressure-volume relationships are likely because the nasal valve and anterior turbinate are structurally different, but both are altered by agents that alter vascular tone. This study determined nasal volume-to-pressure ratio (NVPR) on six healthy nonsmoking subjects by measuring nasal volume by using acoustic rhinometry at pressures ranging between -14 and +14 cmH2O on 3 days: baseline, after intranasal decongestion (oxymetazoline), and congestion (histamine). NVPR was lower in the nasal valve (0.07 +/- 0.01 cm3/cmH2O) than in the anterior portion of the turbinates (0.29 +/- 0.05 cm3/cmH2O; P < 0.005). Oxymetazoline decongestion decreased NVPR in the nasal valve by 23% and NVPR in the anterior portion of the turbinates by 47%. Histamine did not alter NVPR at either site. Nasal resistance changes correlated with changes in nasal valve and anterior turbinate volume. In summary, regional differences in nasal pressure-volume relationships exist and changes occur with pharmacologically induced vascular decongestion.

Human susceptibility to indoor contaminants.

Indoor environmental pollutants can act as irritants, allergens, carcinogens, or infectious agents. This chapter focuses on human susceptibility to indoor environmental pollutants, here defined as inherent factors that alter exposure-response relationships. The host defense system is an important determinant of human susceptibility and is composed of two portions: nonspecific immunity and specific immunity. Pollutants elicit responses from many components of the human host defense system, and human susceptibility results from biologic variability in these components. Nonspecific immunity responds to stressors based on physicochemical properties. Components include mucociliary clearance, the epithelial barrier, airway surface fluid, and neural reflexes. Specific immunity recognizes and responds to unique peptide or carbohydrate sequences present on the foreign agent, and components of the response may include lymphocytes, basophils, mast cells, and immunoglobulins. Irritants typically stimulate nonspecific immunity, allergens stimulate specific immunity, and infecting organisms and carcinogens interact with both. Additional inherent factors that may alter the toxicity of an agent include genetic background, the presence of disease or specific organ pathology, age, gender, body weight, nutritional, hormonal, and central nervous system status. Understanding the basis for human susceptibility to indoor environmental pollutants can assist in implementing practical strategies for managing indoor air quality.