Negative impact of the noseclip on high-frequency respiratory impedance measurements

The noseclip is conventionally used in lung function testing to prevent leakage via the nasal compartments. However, some subjects exhibit a velum-opening reflex which may affect results. We performed forced oscillation measurements at frequencies (8-256 Hz) that include the first antiresonance, comparing the noseclip with a cotton wool nose plug to eliminate upper airway contribution. Three sets of measurements were made in 18 adults: with and without noseclip, and with cotton wool. Velum opening during noseclip measurements was monitored using a nasal pressure transducer. A significantly greater proportion of subjects produced a characteristic distortion to the first antiresonance with the noseclip than with either no noseclip or with cotton wool. Distortion of the spectrum coincided with the transmission of oscillations into the nasal cavity. Thus, the noseclip cannot be used in high-frequency forced oscillation measurements because of the velum reflex. The cotton wool plug offers a simple alternative. This effect has unknown impact in other lung function tests.

Mixed inheritance of equine recurrent airway obstruction

BACKGROUND: Mode of inheritance of equine recurrent airway obstruction (RAO) is unknown. HYPOTHESIS: Major genes are responsible for RAO. ANIMALS: Direct offspring of 2 RAO-affected Warmblood stallions (n = 197; n = 163) and a representative sample of Swiss Warmbloods (n = 401). METHODS: One environmental and 4 genetic models (general, mixed inheritance, major gene, and polygene) were tested for Horse Owner Assessed Respiratory Signs Index (1-4, unaffected to severely affected) by segregation analyses of the 2 half-sib sire families, both combined and separately, using prevalences estimated in a representative sample. RESULTS: In all data sets the mixed inheritance model was most likely to explain the pattern of inheritance. In all 3 datasets the mixed inheritance model did not differ significantly from the general model (P= .62, P= 1.00, and P= .27) but was always better than the major gene model (P < .01) and the polygene model (P < .01). The frequency of the deleterious allele differed considerably between the 2 sire families (P= .23 and P= .06). In both sire families the displacement was large (t= 17.52 and t= 12.24) and the heritability extremely large (h(2)= 1). CONCLUSIONS AND CLINICAL RELEVANCE: Segregation analyses clearly reveal the presence of a major gene playing a role in RAO. In 1 family, the mode of inheritance was autosomal dominant, whereas in the other family it was autosomal recessive. Although the expression of RAO is influenced by exposure to hay, these findings suggest a strong, complex genetic background for RAO.

Genetically determined heterogeneity of lung disease in a mouse model of airway mucus obstruction

Mucus clearance is an important airway innate defense mechanism. Airway-targeted overexpression of the epithelial Na(+) channel β-subunit [encoded by sodium channel nonvoltage gated 1, beta subunit (Scnn1b)] in mice [Scnn1b-transgenic (Tg) mice] increases transepithelial Na(+) absorption and dehydrates the airway surface, which produces key features of human obstructive lung diseases, including mucus obstruction, inflammation, and air-space enlargement. Because the first Scnn1b-Tg mice were generated on a mixed background, the impact of genetic background on disease phenotype in Scnn1b-Tg mice is unknown. To explore this issue, congenic Scnn1b-Tg mice strains were generated on C57BL/6N, C3H/HeN, BALB/cJ, and FVB/NJ backgrounds. All strains exhibited a two- to threefold increase in tracheal epithelial Na(+) absorption, and all developed airway mucus obstruction, inflammation, and air-space enlargement. However, there were striking differences in neonatal survival, ranging from 5 to 80% (FVB/NJupper airway mucus plugging and the levels of Muc5b in bronchoalveolar lavage. The strains also exhibited variable Clara cell necrotic degeneration in neonatal intrapulmonary airways and a variable incidence of pulmonary hemorrhage and lung atelectasis. The spontaneous occurrence of a high surviving BALB/cJ line, which exhibited delayed onset of Na(+) hyperabsorption, provided evidence that: 1) air-space enlargement and postnatal death were only present when Na(+) hyperabsorption occurred early, and 2) inflammation and mucus obstruction developed whenever Na(+) hyperabsorption was expressed. In summary, the genetic context and timing of airway innate immune dysfunction critically determines lung disease phenotype. These mouse strains may be useful to identify key modifier genes and pathways.

Evaluation of coughing and nasal discharge as early indicators for an increased risk to develop equine recurrent airway obstruction (RAO).

BACKGROUND It is often assumed that horses with mild respiratory clinical signs, such as mucous nasal discharge and occasional coughing, have an increased risk of developing recurrent airway obstruction (RAO). HYPOTHESIS Compared to horses without any clinical signs of respiratory disease, those with occasional coughing, mucous nasal discharge, or both have an increased risk of developing signs of RAO (frequent coughing, increased breathing effort, exercise intolerance, or a combination of these) as characterized by the Horse Owner Assessed Respiratory Signs Index (HOARSI 1-4). ANIMALS Two half-sibling families descending from 2 RAO-affected stallions (n = 65 and n = 47) and an independent replication population of unrelated horses (n = 88). METHODS In a retrospective cohort study, standardized information on occurrence and frequency of coughing, mucous nasal discharge, poor performance, and abnormal breathing effort-and these factors combined in the HOARSI-as well as management factors were collected at intervals of 1.3-5 years. RESULTS Compared to horses without clinical signs of respiratory disease (half-siblings 7%; unrelated horses 3%), those with mild respiratory signs developed clinical signs of RAO more frequently: half-siblings with mucous nasal discharge 35% (P < .001, OR: 7.0, sensitivity: 62%, specificity: 81%), with mucous nasal discharge and occasional coughing 43% (P < .001, OR: 9.9, sensitivity: 55%, specificity: 89%); unrelated horses with occasional coughing: 25% (P = .006, OR = 9.7, sensitivity: 75%, specificity: 76%). CONCLUSIONS AND CLINICAL IMPORTANCE Occasional coughing and mucous nasal discharge might represent an increased risk of developing RAO.

Protocol for a randomized, placebo-controlled, double-blind clinical trial investigating sacral neuromodulation for neurogenic lower urinary tract dysfunction

BACKGROUND Sacral neuromodulation has become a well-established and widely accepted treatment for refractory non-neurogenic lower urinary tract dysfunction, but its value in patients with a neurological cause is unclear. Although there is evidence indicating that sacral neuromodulation may be effective and safe for treating neurogenic lower urinary tract dysfunction, the number of investigated patients is low and there is a lack of randomized controlled trials. METHODS AND DESIGN This study is a prospective, randomized, placebo-controlled, double-blind multicenter trial including 4 sacral neuromodulation referral centers in Switzerland. Patients with refractory neurogenic lower urinary tract dysfunction are enrolled. After minimally invasive bilateral tined lead placement into the sacral foramina S3 and/or S4, patients undergo prolonged sacral neuromodulation testing for 3-6 weeks. In case of successful (defined as improvement of at least 50% in key bladder diary variables (i.e. number of voids and/or number of leakages, post void residual) compared to baseline values) prolonged sacral neuromodulation testing, the neuromodulator is implanted in the upper buttock. After a 2 months post-implantation phase when the neuromodulator is turned ON to optimize the effectiveness of neuromodulation using sub-sensory threshold stimulation, the patients are randomized in a 1:1 allocation in sacral neuromodulation ON or OFF. At the end of the 2 months double-blind sacral neuromodulation phase, the patients have a neuro-urological re-evaluation, unblinding takes place, and the neuromodulator is turned ON in all patients. The primary outcome measure is success of sacral neuromodulation, secondary outcome measures are adverse events, urodynamic parameters, questionnaires, and costs of sacral neuromodulation. DISCUSSION It is of utmost importance to know whether the minimally invasive and completely reversible sacral neuromodulation would be a valuable treatment option for patients with refractory neurogenic lower urinary tract dysfunction. If this type of treatment is effective in the neurological population, it would revolutionize the management of neurogenic lower urinary tract dysfunction. TRIAL REGISTRATION TRIAL REGISTRATION NUMBER http://www.clinicaltrials.gov; Identifier: NCT02165774.

Replication and fine-mapping of a QTL for recurrent airway obstruction in European Warmblood horses.

Recurrent airway obstruction (RAO), or 'heaves', is a common performance-limiting allergic respiratory disease of mature horses. It is related to sensitization and exposure to mouldy hay and has a familial basis with a complex mode of inheritance. In a previous study, we detected a QTL for RAO on ECA 13 in a half-sib family of European Warmblood horses. In this study, we genotyped additional markers in the family and narrowed the QTL down to about 1.5 Mb (23.7-25.2 Mb). We detected the strongest association with SNP BIEC2-224511 (24,309,405 bp). We also obtained SNP genotypes in an independent cohort of 646 unrelated Warmblood horses. There was no genome-wide significant association with RAO in these unrelated horses. However, we performed a genotypic association study of the SNPs on ECA 13 in these unrelated horses, and the SNP BIEC2-224511 also showed the strongest association with RAO in the unrelated horses (p(raw) = 0.00037). The T allele at this SNP was associated with RAO both in the family and the unrelated horses. Thus, the association study in the unrelated animals provides independent support for the previously detected QTL. The association study allows further narrowing of the QTL interval to about 0.5 Mb (24.0-24.5 Mb). We sequenced the coding regions of the genes in the critical region but did not find any associated coding variants. Therefore, the causative variant underlying this QTL is likely to be a regulatory mutation.

ERS statement on the multidisciplinary respiratory management of ataxia telangiectasia.

Ataxia telangiectasia (A-T) is a rare, progressive, multisystem disease that has a large number of complex and diverse manifestations which vary with age. Patients with A-T die prematurely with the leading causes of death being respiratory diseases and cancer. Respiratory manifestations include immune dysfunction leading to recurrent upper and lower respiratory infections; aspiration resulting from dysfunctional swallowing due to neurodegenerative deficits; inefficient cough; and interstitial lung disease/pulmonary fibrosis. Malnutrition is a significant comorbidity. The increased radiosensitivity and increased risk of cancer should be borne in mind when requesting radiological investigations. Aggressive proactive monitoring and treatment of these various aspects of lung disease under multidisciplinary expertise in the experience of national multidisciplinary clinics internationally forms the basis of this statement on the management of lung disease in A-T. Neurological management is outwith the scope of this document.

A sensitive, specific, and cost-effective multiplex reverse transcriptase-PCR assay for the detection of seven common respiratory viruses in respiratory samples

Cell culture and direct fluorescent antibody (DFA) assays have been traditionally used for the laboratory diagnosis of respiratory viral infections. Multiplex reverse transcriptase polymerase chain reaction (m-RT-PCR) is a sensitive, specific, and rapid method for detecting several DNIA and RNA viruses in a single specimen. We developed a m-RT-PCR assay that utilizes multiple virus-specific primer pairs in a single reaction mix combined with an enzyme-linked amplicon hybridization assay (ELAHA) using virus-specific probes targeting unique gene sequences for each virus. Using this m-RT-PCR-ELAHA, we examined the presence of seven respiratory viruses in 598 nasopharyngeal aspirate (NPA) samples from patients with suspected respiratory infection. The specificity of each assay was 100%. The sensitivity of the DFA was 79.7% and the combined DFA/culture amplified-DFA (CA-DFA) was 88.6% when compared to the m-RT-PCR-ELAHA. Of the 598 NPA specimens screened by m-RT-PCR-ELAHA, 3% were positive for adenovirus (ADM), 2% for influenza A (Flu A) virus, 0.3% for influenza B (Flu B) virus, 1% for parainfluenza type I virus (PIV1), 1% for parainfluenza type 2 virus (PIV2), 5.5% for parainfluenza type 3 virus (PIV3), and 21% for respiratory syncytial virus (RSV). The enhanced sensitivity, specificity, rapid result turnaround time and reduced expense of the m-RT-PCR-ELAHA compared to DFA and CA-DFA, suggests that this assay would be a significant improvement over traditional assays for the detection of respiratory viruses in a clinical laboratory.

Assessment of disease progression in motor neuron disease

Motor neuron disease (MND) is characterised by progressive deterioration of the corticospinal tract, brainstem, and anterior horn cells of the spinal cord. There is no pathognomonic test for the diagnosis of MND, and physicians rely on clinical criteria-upper and lower motor neuron signs-for diagnosis. The presentations, clinical phenotypes, and outcomes of MND are diverse and have not been combined into a marker of disease progression. No single algorithm combines the findings of functional assessments and rating scales, such as those that assess quality of life, with biological markers of disease activity and findings from imaging and neurophysiological assessments. Here, we critically appraise developments in each of these areas and discuss the potential of such measures to be included in the future assessment of disease progression in patients with MND.

Use of pulse transit time to distinguish respiratory events from tidal breathing in sleeping children

Study objectives: Currently, esophageal pressure monitoring is the "gold standard" measure for inspiratory efforts, hut its invasive nature necessitates a better tolerated and noninvasive method to be used on children. Pulse transit time (PTT) has demonstrated its potential as a noninvasive surrogate marker for inspiratory efforts. The principle velocity determinant of PTT is the change in stiffness of the arterial wall and is inversely correlated to BP. Moreover, PTT has been shown to identify changes in inspiratory effort via the BP fluctuations induced by negative pleural pressure swings. In this study, the capability of PTT to classify respiratory, events during sleep as either central or obstructive in nature was investigated. Setting and participants: PTT measure was used in adjunct to routine overnight polysomnographic studies performed on 33 children (26 boys and 7 girls; mean +/- SD age, 6.7 +/- 3.9 years). The accuracy of PTT measurements was then evaluated against scored corresponding respiratory events in the polysomnography recordings. Results: Three hundred thirty-four valid respiratory events occurred and were analyzed. One hundred twelve obstructive events (OEs) showed a decrease in mean PTT over a 10-sample window that had a probability of being correctly ranked below the baseline PTT during tidal breathing of 0.92 (p < 0.005); 222 central events (CEs) showed a decrease in the variance of PTT over a 10-sample window that had a probability of being ranked below the baseline PTT of 0.94 (p < 0.005). This indicates that, at a sensitivity of 0.90, OEs can be detected with a specificity of 0.82 and CEs can be detected with a specificity of 0.80. Conclusions: PTT is able to categorize CEs and OEs accordingly in the absence of motion artifacts, including hypopneas. Hence, PTT shows promise to differentiate respiratory, events accordingly and can be an important diagnostic tool in pediatric respiratory sleep studies.< 0.005); 222 central events (CEs) showed a decrease in the variance of PTT over a 10-sample window that had a probability of being ranked below the baseline PTT of 0.94 (p < 0.005). This indicates that, at a sensitivity of 0.90, OEs can be detected with a specificity of 0.82 and CEs can be detected with a specificity of 0.80. Conclusions: PTT is able to categorize CEs and OEs accordingly in the absence of motion artifacts, including hypopneas. Hence, PTT shows promise to differentiate respiratory, events accordingly and can be an important diagnostic tool in pediatric respiratory sleep studies.');"

The relationship between chronic cough and paradoxical vocal fold movement: A review of the literature

Chronic cough (CC) and paradoxical vocal fold movement (PVFM) are debilitating conditions. PVFM has been given many labels,(1) including vocal cord dysfunction, Munchausen's stridor, functional inspiratory stridor, nonorganic functional or psychogenic upper airway obstruction, factitious asthma, psychogenic stridor, emotional laryngeal wheezing, and episodic laryngeal dyskinesia. 3 Although CC and PVFM have been considered separate entities in many reports, there is preliminary support for the notion that there may be an underlying link between these two conditions. Speech pathologists have become increasingly involved in the treatment of these patients and therefore need to understand the theoretical background of these disorders, the pathophysiological links between the two, and the impact of voice disorders on these populations. The aim of this article is to review the current literature on CC and PVFM from a speech pathology perspective to provide a model for defining and conceptualizing the disorders and to provide a framework for management and future research.

Differentiating responses to obstructive sleep apnoea using pulse transit time

Conventional overnight polysomnography (PSG) used to determine the respiratory behaviour during sleep can be a complex and expensive procedure. Pulse transit time analysis (PTT) has shown potential to detect obstructive apnoeic and hypopnoeic events in adults. This study was undertaken to determine the potential of PTT to differentiate responses to upper airway obstruction. 103 obstructive respiratory events occurred in PSG studies performed on 11 children (10 male and 1 female, mean age 7.5years). PTT measurements were evaluated against the corresponding PSG results pre-scored by 2 blinded observers. Broadly, there were 2 types of responses. They can be either short period of rapid PTT decreases (Type 1) or prolonged but gradual PTT decreases (Type 2). Type 1 obstructive events showed a mean change of 51.77% (p

A three dimensional surface measurement and reconstruction system for respiratory function analysis

Respiration is a complex activity. If the relationship between all neurological and skeletomuscular interactions was perfectly understood, an accurate dynamic model of the respiratory system could be developed and the interaction between different inputs and outputs could be investigated in a straightforward fashion. Unfortunately, this is not the case and does not appear to be viable at this time. In addition, the provision of appropriate sensor signals for such a model would be a considerable invasive task. Useful quantitative information with respect to respiratory performance can be gained from non-invasive monitoring of chest and abdomen motion. Currently available devices are not well suited in application for spirometric measurement for ambulatory monitoring. A sensor matrix measurement technique is investigated to identify suitable sensing elements with which to base an upper body surface measurement device that monitors respiration. This thesis is divided into two main areas of investigation; model based and geometrical based surface plethysmography. In the first instance, chapter 2 deals with an array of tactile sensors that are used as progression of existing and previously investigated volumetric measurement schemes based on models of respiration. Chapter 3 details a non-model based geometrical approach to surface (and hence volumetric) profile measurement. Later sections of the thesis concentrate upon the development of a functioning prototype sensor array. To broaden the application area the study has been conducted as it would be fore a generically configured sensor array. In experimental form the system performance on group estimation compares favourably with existing system on volumetric performance. In addition provides continuous transient measurement of respiratory motion within an acceptable accuracy using approximately 20 sensing elements. Because of the potential size and complexity of the system it is possible to deploy it as a fully mobile ambulatory monitoring device, which may be used outside of the laboratory. It provides a means by which to isolate coupled physiological functions and thus allows individual contributions to be analysed separately. Thus facilitating greater understanding of respiratory physiology and diagnostic capabilities. The outcome of the study is the basis for a three-dimensional surface contour sensing system that is suitable for respiratory function monitoring and has the prospect with future development to be incorporated into a garment based clinical tool.

A utilização das análises cefalométricas no diagnóstico dos distúrbios do sono

A Síndrome da Apneia e Hipopneia Obstrutiva do Sono (SAHOS) é uma doença crónica, de carácter progressivo, que atinge cerca de 4% da população adulta. A obstrução parcial ou total das vias aéreas superiores durante o sono pode provocar quadros de hipopneia (uma redução do fluxo aéreo) ou apneia (cessação completa do fluxo aéreo). Os pacientes queixam-se de sonolência diurna excessiva, ronco durante a noite e além destes problemas sociais a preocupação pela redução de funções cognitivas que se podem desencadear, como memória, atenção, hipertensão pulmonar e insuficiência cardíaca. O Médico Dentista está habilitado para avaliar o espaço aéreo oro e nasofaringeo e diagnosticar, além da necessidade de correções dentárias, a presença de obstruções das Vias Aereas Superiores (VAS) orientando assim o seu tratamento. Além do exame clínico, o diagnóstico de distúrbios respiratórios do sono é baseado na história clínica, exame físico e confirmado através da polissonografia e da análise cefalométrica. Esta tem sido considerada como um método importante no diagnóstico, fornecendo características craniofaciais que permitem verificar a existência de pré-disposição de SAHOS. As avaliações com cefalometrias obtidas em telerradiografias em norma lateral é um recurso essencial para realizar o diagnóstico de distúrbios respiratórios do sono, desde que o profissional tenha domínio da técnica e da sua interpretação. Estes distúrbios são caracterizados por diferentes graus de diminuição do espaço das vias aéreas superiores, causado por factores anatómicos e funcionais, que podem ser analisados pelo profissional. A intervenção precoce torna-se crucial, pela diminuição da morbilidade, melhores resultados no tratamento, diminuição de gastos nos serviços de saúde e melhor qualidade de vida do paciente. O presente trabalho teve por objectivo realizar uma revisão bibliográfica sobre a importância da avaliação das vias aéreas superiores através da análise de grandezas cefalométricas obtidas de telerradiografias em norma lateral como padrão de diagnóstico para a identificação de distúrbios respiratórios do sono.

Flexible bronchoscopy contribution in the approach of diagnosis and treatment of children’s respiratory diseases: the experience of a unique pediatric unit in Tunisia.

Objective: Our study aimed at assessing the role of flexible bronchoscopy (FB) in improving diagnosis and management of children’s respiratory conditions in the pediatric unit of FB, newly created and unique in Tunisia. Methods: Retrospective study including all the FB achieved in our pediatric unit from 2009 to 2014. Results: We performed 365 FB in 333 patients aged 46 months on average (1 month - 15 years), often under conscious anesthesia (81.6%). FB was performed for diagnostic purposes in 341 cases and for therapeutic purposes in 24 cases. Eight anatomical abnormalities were revealed in 22 patients. An intraluminal bronchial obstruction was found in 71 FB, mainly due to a foreign body (n=36). A vascular anomaly was responsible for nine cases out of 17 extraluminal obstructions. Airways malacia was observed in 60 FB. Bronchoalveolar lavage was performed in 196 cases. It was determinant in 43.9% of the cases. FB was of great diagnostic value in 74.8% of the cases. It influenced the management of the patients in 58% of the cases. The FB for therapeutic purposes was beneficial in all cases. Few complications occurred (5.5%). Conclusion: FB is a safe tool providing precious diagnostic and/or therapeutic help for the clinician. Keywords: