Forecasting life expectancy, years of life lost, and all-cause and cause-specific mortality for 250 causes of death: reference and alternative scenarios for 2016-40 for 195 countries and territories.

BACKGROUND: Understanding potential trajectories in health and drivers of health is crucial to guiding long-term investments and policy implementation. Past work on forecasting has provided an incomplete landscape of future health scenarios, highlighting a need for a more robust modelling platform from which policy options and potential health trajectories can be assessed. This study provides a novel approach to modelling life expectancy, all-cause mortality and cause of death forecasts -and alternative future scenarios-for 250 causes of death from 2016 to 2040 in 195 countries and territories. METHODS: We modelled 250 causes and cause groups organised by the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) hierarchical cause structure, using GBD 2016 estimates from 1990-2016, to generate predictions for 2017-40. Our modelling framework used data from the GBD 2016 study to systematically account for the relationships between risk factors and health outcomes for 79 independent drivers of health. We developed a three-component model of cause-specific mortality: a component due to changes in risk factors and select interventions; the underlying mortality rate for each cause that is a function of income per capita, educational attainment, and total fertility rate under 25 years and time; and an autoregressive integrated moving average model for unexplained changes correlated with time. We assessed the performance by fitting models with data from 1990-2006 and using these to forecast for 2007-16. Our final model used for generating forecasts and alternative scenarios was fitted to data from 1990-2016. We used this model for 195 countries and territories to generate a reference scenario or forecast through 2040 for each measure by location. Additionally, we generated better health and worse health scenarios based on the 85th and 15th percentiles, respectively, of annualised rates of change across location-years for all the GBD risk factors, income per person, educational attainment, select intervention coverage, and total fertility rate under 25 years in the past. We used the model to generate all-cause age-sex specific mortality, life expectancy, and years of life lost (YLLs) for 250 causes. Scenarios for fertility were also generated and used in a cohort component model to generate population scenarios. For each reference forecast, better health, and worse health scenarios, we generated estimates of mortality and YLLs attributable to each risk factor in the future. FINDINGS: Globally, most independent drivers of health were forecast to improve by 2040, but 36 were forecast to worsen. As shown by the better health scenarios, greater progress might be possible, yet for some drivers such as high body-mass index (BMI), their toll will rise in the absence of intervention. We forecasted global life expectancy to increase by 4·4 years (95% UI 2·2 to 6·4) for men and 4·4 years (2·1 to 6·4) for women by 2040, but based on better and worse health scenarios, trajectories could range from a gain of 7·8 years (5·9 to 9·8) to a non-significant loss of 0·4 years (-2·8 to 2·2) for men, and an increase of 7·2 years (5·3 to 9·1) to essentially no change (0·1 years [-2·7 to 2·5]) for women. In 2040, Japan, Singapore, Spain, and Switzerland had a forecasted life expectancy exceeding 85 years for both sexes, and 59 countries including China were projected to surpass a life expectancy of 80 years by 2040. At the same time, Central African Republic, Lesotho, Somalia, and Zimbabwe had projected life expectancies below 65 years in 2040, indicating global disparities in survival are likely to persist if current trends hold. Forecasted YLLs showed a rising toll from several non-communicable diseases (NCDs), partly driven by population growth and ageing. Differences between the reference forecast and alternative scenarios were most striking for HIV/AIDS, for which a potential increase of 120·2% (95% UI 67·2-190·3) in YLLs (nearly 118 million) was projected globally from 2016-40 under the worse health scenario. Compared with 2016, NCDs were forecast to account for a greater proportion of YLLs in all GBD regions by 2040 (67·3% of YLLs [95% UI 61·9-72·3] globally); nonetheless, in many lower-income countries, communicable, maternal, neonatal, and nutritional (CMNN) diseases still accounted for a large share of YLLs in 2040 (eg, 53·5% of YLLs [95% UI 48·3-58·5] in Sub-Saharan Africa). There were large gaps for many health risks between the reference forecast and better health scenario for attributable YLLs. In most countries, metabolic risks amenable to health care (eg, high blood pressure and high plasma fasting glucose) and risks best targeted by population-level or intersectoral interventions (eg, tobacco, high BMI, and ambient particulate matter pollution) had some of the largest differences between reference and better health scenarios. The main exception was sub-Saharan Africa, where many risks associated with poverty and lower levels of development (eg, unsafe water and sanitation, household air pollution, and child malnutrition) were projected to still account for substantive disparities between reference and better health scenarios in 2040. INTERPRETATION: With the present study, we provide a robust, flexible forecasting platform from which reference forecasts and alternative health scenarios can be explored in relation to a wide range of independent drivers of health. Our reference forecast points to overall improvements through 2040 in most countries, yet the range found across better and worse health scenarios renders a precarious vision of the future-a world with accelerating progress from technical innovation but with the potential for worsening health outcomes in the absence of deliberate policy action. For some causes of YLLs, large differences between the reference forecast and alternative scenarios reflect the opportunity to accelerate gains if countries move their trajectories toward better health scenarios-or alarming challenges if countries fall behind their reference forecasts. Generally, decision makers should plan for the likely continued shift toward NCDs and target resources toward the modifiable risks that drive substantial premature mortality. If such modifiable risks are prioritised today, there is opportunity to reduce avoidable mortality in the future. However, CMNN causes and related risks will remain the predominant health priority among lower-income countries. Based on our 2040 worse health scenario, there is a real risk of HIV mortality rebounding if countries lose momentum against the HIV epidemic, jeopardising decades of progress against the disease. Continued technical innovation and increased health spending, including development assistance for health targeted to the world's poorest people, are likely to remain vital components to charting a future where all populations can live full, healthy lives. FUNDING: Bill & Melinda Gates Foundation.

Quantifying robustness of the /t/-/k/ contrast using a single, static spectral feature.

Dynamic spectral shape features accurately classify /t/ and /k/ productions across speakers and contexts. This paper shows that word-initial /t/ and /k/ tokens produced by 21 adults can be differentiated using a single, static spectral feature when spectral energy concentration is considered relative to expectations within a given speaker and vowel context. Centroid and peak frequency-calculated from both acoustic and psychoacoustic spectra-were compared to determine whether one feature could reliably differentiate /t/ and /k/, and, if so, which feature best differentiated them. Centroid frequency from both acoustic and psychoacoustic spectra accurately classified productions of /t/ and /k/.

National spending on health by source for 184 countries between 2013 and 2040.

BACKGROUND: A general consensus exists that as a country develops economically, health spending per capita rises and the share of that spending that is prepaid through government or private mechanisms also rises. However, the speed and magnitude of these changes vary substantially across countries, even at similar levels of development. In this study, we use past trends and relationships to estimate future health spending, disaggregated by the source of those funds, to identify the financing trajectories that are likely to occur if current policies and trajectories evolve as expected. METHODS: We extracted data from WHO's Health Spending Observatory and the Institute for Health Metrics and Evaluation's Financing Global Health 2015 report. We converted these data to a common purchasing power-adjusted and inflation-adjusted currency. We used a series of ensemble models and observed empirical norms to estimate future government out-of-pocket private prepaid health spending and development assistance for health. We aggregated each country's estimates to generate total health spending from 2013 to 2040 for 184 countries. We compared these estimates with each other and internationally recognised benchmarks. FINDINGS: Global spending on health is expected to increase from US$7·83 trillion in 2013 to $18·28 (uncertainty interval 14·42-22·24) trillion in 2040 (in 2010 purchasing power parity-adjusted dollars). We expect per-capita health spending to increase annually by 2·7% (1·9-3·4) in high-income countries, 3·4% (2·4-4·2) in upper-middle-income countries, 3·0% (2·3-3·6) in lower-middle-income countries, and 2·4% (1·6-3·1) in low-income countries. Given the gaps in current health spending, these rates provide no evidence of increasing parity in health spending. In 1995 and 2015, low-income countries spent $0·03 for every dollar spent in high-income countries, even after adjusting for purchasing power, and the same is projected for 2040. Most importantly, health spending in many low-income countries is expected to remain low. Estimates suggest that, by 2040, only one (3%) of 34 low-income countries and 36 (37%) of 98 middle-income countries will reach the Chatham House goal of 5% of gross domestic product consisting of government health spending. INTERPRETATION: Despite remarkable health gains, past health financing trends and relationships suggest that many low-income and lower-middle-income countries will not meet internationally set health spending targets and that spending gaps between low-income and high-income countries are unlikely to narrow unless substantive policy interventions occur. Although gains in health system efficiency can be used to make progress, current trends suggest that meaningful increases in health system resources will require concerted action. FUNDING: Bill & Melinda Gates Foundation.

The Acoustics of Word-Initial Fricatives and Their Effect on Word-Level Intelligibility in Children With Bilateral Cochlear Implants.

OBJECTIVES: Previous research has found that relative to their peers with normal hearing (NH), children with cochlear implants (CIs) produce the sibilant fricatives /s/ and /∫/ less accurately and with less subphonemic acoustic contrast. The present study sought to further investigate these differences across groups in two ways. First, subphonemic acoustic properties were investigated in terms of dynamic acoustic features that indexed more than just the contrast between /s/ and /∫/. Second, the authors investigated whether such differences in subphonemic acoustic contrast between sibilant fricatives affected the intelligibility of sibilant-initial single word productions by children with CIs and their peers with NH. DESIGN: In experiment 1, productions of /s/ and /∫/ in word-initial prevocalic contexts were elicited from 22 children with bilateral CIs (aged 4 to 7 years) who had at least 2 years of CI experience and from 22 chronological age-matched peers with NH. Acoustic features were measured from 17 points across the fricatives: peak frequency was measured to index the place of articulation contrast; spectral variance and amplitude drop were measured to index the degree of sibilance. These acoustic trajectories were fitted with growth-curve models to analyze time-varying spectral change. In experiment 2, phonemically accurate word productions that were elicited in experiment 1 were embedded within four-talker babble and played to 80 adult listeners with NH. Listeners were asked to repeat the words, and their accuracy rate was used as a measure of the intelligibility of the word productions. Regression analyses were run to test which acoustic properties measured in experiment 1 predicted the intelligibility scores from experiment 2. RESULTS: The peak frequency trajectories indicated that the children with CIs produced less acoustic contrast between /s/ and /∫/. Group differences were observed in terms of the dynamic aspects (i.e., the trajectory shapes) of the acoustic properties. In the productions by children with CIs, the peak frequency and the amplitude drop trajectories were shallower, and the spectral variance trajectories were more asymmetric, exhibiting greater increases in variance (i.e., reduced sibilance) near the fricative-vowel boundary. The listeners' responses to the word productions indicated that when produced by children with CIs, /∫/-initial words were significantly more intelligible than /s/-initial words. However, when produced by children with NH, /s/-initial words and /∫/-initial words were equally intelligible. Intelligibility was partially predicted from the acoustic properties (Cox & Snell pseudo-R > 0.190), and the significant predictors were predominantly dynamic, rather than static, ones. CONCLUSIONS: Productions from children with CIs differed from those produced by age-matched NH controls in terms of their subphonemic acoustic properties. The intelligibility of sibilant-initial single-word productions by children with CIs is sensitive to the place of articulation of the initial consonant (/∫/-initial words were more intelligible than /s/-initial words), but productions by children with NH were equally intelligible across both places of articulation. Therefore, children with CIs still exhibit differential production abilities for sibilant fricatives at an age when their NH peers do not.

Spectral dynamics of sibilant fricatives are contrastive and language specific.

Previous research has extensively investigated the spectral properties of sibilant fricatives with little consideration to how these properties vary over time. To investigate such spectro-temporal variation, productions of English /s/ and /ʃ/ and of Japanese /s/ and /ɕ/ in word-initial, prevocalic position were elicited from adult native speakers. The spectral dynamics of these productions were analyzed in terms of a psychoacoustic measure of peak frequency: "peak ERBN number." Peak ERBN number was computed at 17 evenly spaced points across each fricative production. The resulting peak ERBN number trajectories were analyzed with orthogonal polynomial growth-curve models, to determine how peak frequency varied temporally within each fricative. Three analyses compared (1) the English sibilants to each other, (2) the Japanese sibilants to each other, and (3) English /s/ to Japanese /s/. The results indicated that, in both English and Japanese, the sibilant fricatives differ acoustically in terms of both static (i.e., overall level) and dynamic (i.e., shape) aspects of the peak ERBN number trajectories. Furthermore, English /s/ and Japanese /s/ exhibited language-specific differences in the shape, but not overall level, of peak ERBN number trajectories.

A comparison of spectral estimation methods for the analysis of sibilant fricatives.

It has been argued that, to ensure accurate spectral feature estimates for sibilants, the spectral estimation method should include a low-variance spectral estimator; however, no empirical evaluation of estimation methods in terms of feature estimates has been given. The spectra of /s/ and /ʃ/ were estimated with different methods that varied the pre-emphasis filter and estimator. These methods were evaluated in terms of effects on two features (centroid and degree of sibilance) and on the detection of four linguistic contrasts within these features. Estimation method affected the spectral features but none of the tested linguistic contrasts.

Relationship between early phonological processing and later phonological awareness: Evidence from nonword repetition.

This study investigated whether individual differences in vocabulary size, speech perception and production, and nonword repetition in 2½ to 3-year-old children predicted phonological awareness two years later. One hundred twenty-two children were tested twice. During the first testing period, we measured children's receptive vocabulary, speech perception, nonword repetition, and articulation. At the second testing period, we measured children's phonological awareness. The best predictors of phonological awareness at age 5 were receptive vocabulary and a measure of phonological processing derived from performance on the nonword repetition task. The results of this study suggest that nonword repetition accuracy can be used to index implicit phonological awareness at an age when children are too young to perform explicit phonological awareness tasks reliably.

A Framework for Predicting Impactability of Digital Care Management Using Machine Learning Methods.

Digital care management programs can reduce health care costs and improve quality of care. However, it is unclear how to target patients who are most likely to benefit from these programs ex ante, a shortcoming of current "risk score"-based approaches across many interventions. This study explores a framework to define impactability by using machine learning (ML) models to identify those patients most likely to benefit from a digital health intervention for care management. Anonymized insurance claims data were used from a commercially insured population across several US states and combined with inferred sociodemographic data. The approach involves creating 2 models and the comparative analysis of the methodologies and performances therein. The authors first train a cost prediction model to calculate the differences in predicted (without intervention) versus actual (with onboarding onto digital health platform) health care expenditures for patients (N = 5600). This enables classification impactability if differences in predicted versus actual costs meet a predetermined threshold. Several random forest and logistic regression machine learning models were then trained to accurately categorize new patients as impactable versus not impactable. These parameters are modified through grid search to define the parameters that deliver optimal performance, reaching an overall sensitivity of 0.77 and specificity of 0.65 among all models. This approach shows that impactability for a digital health intervention can be successfully defined using ML methods, thus enabling efficient allocation of resources. This framework is generalizable to analyzing impactability of any intervention and can contribute to realizing closed-loop feedback systems for continuous improvement in health care.

Computing low-dimensional representations of speech from socio-auditory structures for phonetic analyses.

Low-dimensional representations of speech data, such as formant values extracted by linear predictive coding analysis or spectral moments computed from whole spectra viewed as probability distributions, have been instrumental in both phonetic and phonological analyses over the last few decades. In this paper, we present a framework for computing low-dimensional representations of speech data based on two assumptions: that speech data represented in high-dimensional data spaces lie on shapes called manifolds that can be used to map speech data to low-dimensional coordinate spaces, and that manifolds underlying speech data are generated from a combination of language-specific lexical, phonological, and phonetic information as well as culture-specific socio-indexical information that is expressed by talkers of a given speech community. We demonstrate the basic mechanics of the framework by carrying out an analysis of children's productions of sibilant fricatives relative to those of adults in their speech community using the phoneigen package - a publicly available implementation of the framework. We focus the demonstration on enumerating the steps for constructing manifolds from data and then using them to map the data to a low-dimensional space, explicating how manifold structure affects the learned low-dimensional representations, and comparing the use of these representations against standard acoustic features in a phonetic analysis. We conclude with a discussion of the framework's underlying assumptions, its broader modeling potential, and its position relative to recent advances in the field of representation learning.

Methods for eliciting, annotating, and analyzing databases for child speech development.

Methods from automatic speech recognition (ASR), such as segmentation and forced alignment, have facilitated the rapid annotation and analysis of very large adult speech databases and databases of caregiver-infant interaction, enabling advances in speech science that were unimaginable just a few decades ago. This paper centers on two main problems that must be addressed in order to have analogous resources for developing and exploiting databases of young children's speech. The first problem is to understand and appreciate the differences between adult and child speech that cause ASR models developed for adult speech to fail when applied to child speech. These differences include the fact that children's vocal tracts are smaller than those of adult males and also changing rapidly in size and shape over the course of development, leading to between-talker variability across age groups that dwarfs the between-talker differences between adult men and women. Moreover, children do not achieve fully adult-like speech motor control until they are young adults, and their vocabularies and phonological proficiency are developing as well, leading to considerably more within-talker variability as well as more between-talker variability. The second problem then is to determine what annotation schemas and analysis techniques can most usefully capture relevant aspects of this variability. Indeed, standard acoustic characterizations applied to child speech reveal that adult-centered annotation schemas fail to capture phenomena such as the emergence of covert contrasts in children's developing phonological systems, while also revealing children's nonuniform progression toward community speech norms as they acquire the phonological systems of their native languages. Both problems point to the need for more basic research into the growth and development of the articulatory system (as well as of the lexicon and phonological system) that is oriented explicitly toward the construction of age-appropriate computational models.

Airway obstruction by granulation tissue within a fenestrated tracheotomy tube: case report.

Complications of tracheotomy tube placement can be categorized as intraoperative, early postoperative, and late postoperative. Among the late complications is the development of granulation tissue. We describe one of the few reported cases of granulation tissue that formed within a fenestrated tracheotomy tube. In this case, the granulation tissue grew through the fenestrations, obliterated the tracheal lumen, and tethered the tube to the trachea itself. As a result, the patient required emergency treatment to restore airway patency.

Human papillomavirus (HPV) transcripts in malignant inverted papilloma are from integrated HPV DNA.

OBJECTIVES: The objectives of the study were to detect human papillomavirus (HPV) sequences in nasal inverted papilloma (IP) lesions and to determine whether HPV is involved in the progression of IP to sinonasal squamous cell carcinoma (SCC). STUDY DESIGN: A retrospective study was performed on 14 patients diagnosed with IP within the last 12 years. Three of these 14 patients developed SCC. METHODS: Eighteen formalin-fixed, paraffin-embedded tissue blocks were obtained for these 14 patients. After DNA extraction, polymerase chain reaction (PCR) was performed, followed by hybridization using HPV 6, 11, 16, 18, 31, 33, 35, 45, and 52 specific DNA probes, in an attempt to identify HPV type in each specimen. After RNA extraction, the integration status of the HPV genome was evaluated based on the relative abundance of E7 and E5 viral transcripts, assessed by quantitative real-time PCR. RESULTS: HPV sequences were detected in samples from 3 of the 14 patients with IP. Of the three patients with SCC, HPV sequences were detected in two patients, whereas one patient was negative for the oligoprobes tested. Of the 11 patients diagnosed only with IP, 1 patient was positive for HPV DNA (HPV type 11). This difference in HPV positivity between IP and SCC was not statistically significant (P = .09, Fisher's Exact test, two tailed). Viral transcripts were detected in both patients with SSC who were HPV positive. Because HPV early transcripts are polycistronic, loss of 3' transcript sequences (E5) and retention of 5' sequences (E7) indicates integration. One of the SSC containing HPV 18 sequences showed a E7/E5 ratio of 776:1. The other SSC showed E7 transcripts and an absence of E5 transcripts CONCLUSION: HPV transcripts were present in SCC positive for HPV, and the relative level of E7 to E5 transcripts indicates integration of the viral genome. These findings are suggestive of HPV having an active role in the lesion. More extensive studies are needed to determine the exact role of HPV in IP and progression to SCC.

Quantifying the Robustness of the English Sibilant Fricative Contrast in Children.

PURPOSE: Four measures of children's developing robustness of phonological contrast were compared to see how they correlated with age, vocabulary size, and adult listeners' correctness ratings. METHOD: Word-initial sibilant fricative productions from eighty-one 2- to 5-year-old children and 20 adults were phonetically transcribed and acoustically analyzed. Four measures of robustness of contrast were calculated for each speaker on the basis of the centroid frequency measured from each fricative token. Productions that were transcribed as correct from different children were then used as stimuli in a perception experiment in which adult listeners rated the goodness of each production. RESULTS: Results showed that the degree of category overlap, quantified as the percentage of a child's productions whose category could be correctly predicted from the output of a mixed-effects logistic regression model, was the measure that correlated best with listeners' goodness judgments. CONCLUSIONS: Even when children's productions have been transcribed as correct, adult listeners are sensitive to within-category variation quantified by the child's degree of category overlap. Further research is needed to explore the relationship between the age of a child and adults' sensitivity to different types of within-category variation in children's speech.

Integration of human papillomavirus type 11 in recurrent respiratory papilloma-associated cancer.

OBJECTIVES/HYPOTHESIS: The main objective was to demonstrate that human papillomavirus (HPV) type 11 is an aggressive virus that plays a significant role in the development of laryngeal cancer in patients with a history of recurrent respiratory papillomatosis (RRP). We have done so by preliminary investigation into the molecular mechanism underlying the malignant transformation of RRP to invasive squamous cell carcinoma. STUDY DESIGN: An experimental, nonrandomized, retrospective study using tissue specimens from nine patients with a history of RRP that progressed to laryngeal or bronchogenic cancer was performed. METHODS: DNA and RNA were extracted from 20 formalin-fixed, paraffin-embedded specimens from six patients with a history of early onset RRP and laryngeal cancer and from three patients with early onset RRP and bronchogenic cancer. Polymerase chain reaction (PCR) was performed on DNA to determine the HPV type in each specimen. Reverse-transcriptase PCR specific for virus transcripts was performed on RNA to determine whether the viral genome was integrated into the host genome. RESULTS: HPV-11 but not HPV-6, 16, or 18 was found in all of the laryngeal and bronchogenic cancers in patients with a history of early onset RRP in this study. RNA, sufficiently intact for examination, was obtained from seven patients. Analysis of HPV 11 transcripts revealed integration of the viral genome in three of seven patients. CONCLUSIONS: HPV type 6 and 11 are considered "low-risk" viruses and are not associated with genital cancers, as are HPV types 16 and 18. However, our data suggests that HPV type 11 is an aggressive virus in laryngeal papilloma that should be monitored in patients with RRP.

HLA-DQ alleles in white and African American patients with juvenile-onset recurrent respiratory papillomatosis.

OBJECTIVE: To determine HLA-DQalpha and -DQbeta1 allele associations in juvenile-onset recurrent respiratory papillomatosis (RRP) for risk, disease course, and human papillomavirus type. DESIGN: A nonrandomized controlled study was performed on DNA extracted from papilloma specimens of children with a history of RRP, and from peripheral blood of African American and white children without RRP. The frequencies of DQalpha and DQbeta1 alleles were compared between patients and ethnically matched controls. SUBJECTS: Records of 48 children treated for RRP at Children's Hospital of Michigan in Detroit (26 African American and 22 white) were reviewed. Control subjects consisted of 80 African American and 80 white children seen at the hospital for conditions other than RRP. RESULTS: African American and white patients with DQbeta1*050X (not *0501, *0502, *0503, *0504, or *0505) were at higher risk to develop RRP than controls (P =.01 and.03, respectively). DQbeta1*0402 was protective for African Americans (P =.01). Whites with DQalpha*0102 were at risk for RRP (P =.03). This allele was associated with disease remission in African Americans (P =.03). DQalpha*0101/0104 conferred protection in whites (P =.047). No association was seen for allele frequency and human papillomavirus type. Whites with haplotype DQalpha*0501/DQbeta1*0201 were at high risk for RRP (P =.002). No relationships were seen for African Americans or whites between haplotype frequencies and disease course or human papillomavirus type. CONCLUSIONS: HLA-DQalpha and -DQbeta1 alleles occur at different frequencies in African American and white children with RRP than controls. Specific alleles influence risk for RRP. Allele and haplotype frequencies have some influence on disease course, but were independent of human papillomavirus type.

Laryngeal effects of antigen stimulation challenge with perennial allergen Dermatophagoides pteronyssinus.

OBJECTIVE: We conducted a pilot study to assess the effects of antigen stimulation on the appearance and function of the larynx. STUDY DESIGN AND SUBJECTS: The prospective, double-blind, randomized study included 9 adult patients with a skin-prick test positive for Dermatophagoides pteronyssinus. MAIN OUTCOME MEASURES: Subjects were blindly challenged via nebulizer with either an active antigenic suspension or placebo. Baseline and 30-minute evaluations of the larynx were performed. Assessments included subjective voice and videostroboscopic assessments, acoustic analysis of voice, speech aerodynamic testing, and allergy and voice handicap questionnaires. RESULTS: Although both inflammation and increased mucus were noted, there were no significant differences between the antigen- and placebo-exposed subjects on any of the measures obtained. CONCLUSIONS: Our preliminary investigation was not successful in demonstrating a direct causal relationship between antigen exposure and physical or functional changes in the larynx. Future studies will involve modifications to our current methodology, including increasing the concentration of antigen, prolonging the exposure time, and observing for late phase responses.

Effects of sequential Dermatophagoides pteronyssinus antigen stimulation on anatomy and physiology of the larynx.

The goal of this investigation was to study the effects of sequential dust mite antigen stimulation on the appearance and function of the larynx. To that end, we designed a randomized, placebo-controlled, double-blind, prospective analysis of adults who had tested positive for perennial dust mite allergy. The larynx of patients who received the active antigen was challenged directly with a low (1:100) and a high (1:40) concentration of the dust mite allergen via an oral nebulizer. Voice laboratory assessment tools included voice and allergy questionnaires, videostroboscopic examination of the larynx, acoustic and speech aerodynamic analyses, and digital audio voice recordings. The study was prematurely terminated after 2 patients had been treated with the highest concentration of the antigenic suspension because of adverse effects, including chest tightness, coughing, and voice difficulties. Both of these patients had demonstrated viscous endolaryngeal secretions and vocal fold edema on videostroboscopy. No reactions were noted at the lower concentration of antigen exposure or in 1 control patient who completed the study. We believe that our findings, as preliminary as they are, may serve as an initial template for the differential diagnosis and treatment of other patients with inhalant allergies who present with chief complaints suggestive of allergic laryngitis.

Physiological change in nasal patency in response to changes in posture, temperature, and humidity measured by acoustic rhinometry.

BACKGROUND: Acoustic rhinometry has been used to assess nasal patency and to calculate nasal cavity volume. This study used acoustic rhinometry to assess changes in nasal patency after alterations in posture, unilateral mechanical obstruction, temperature, and humidity. METHODS: Eight healthy adult volunteer subjects underwent acoustic rhinometry during the following conditions: (1) sitting position (control), (2) supine position, (3) left lateral recumbent position, (4) nostril unilaterally mechanically blocked, (5) ice pack on neck, (6) drinking cold water, (7) drinking hot water, (8) nasal nebulizer, and (9) oxymetazoline decongestant. RESULTS: Two distinct patterns emerged based on the total nasal cavity volumes in response to the decongestant. Subjects with initial unilateral nasal cavity volumes near the mean had an expected increase in total volume after the topical decongestant administration. There were two subjects with initial volumes of 1 SD above the mean that had a paradoxical decrease in total volume in response to the decongestant. In all subjects, there was a significant decrease in the volume of each of the nasal cavities in response to ingestion of hot water at 1 minute. There was a significant decrease in the volume of the smaller of the two nasal cavities in response to nebulizer treatment and hot water ingestion at 5 minutes. Total nasal cavity volume changes were not significant for any of the variables. CONCLUSION: Changes in nasal cavity volumes were detected by acoustic rhinometry after alterations in posture, unilateral mechanical obstruction, temperature, and humidity. Nebulizer treatment and hot water ingestion caused a significant decrease in nasal volume. The nose of a healthy patient was able to adapt to environmental and physiological changes to maintain a consistent total nasal volume within 15 minutes.