Studies on Parainfluenza Type 2 and 4 Viruses Obtained from Patients with Common Colds

Four agents which were obtained from adults with common colds were cultivated and identified—one was influenza type B and the others were parainfluenza viruses of types 2 and 4. Their cultivation was assisted by the use of organ cultures of human embryo tracheal or nasal epithelium. They infected and caused typical common colds in volunteers.     

Effect of topical prostaglandins on nasal patency in man.

The effect of prostaglandin E1 and 17 phenyl trinor PGE2 on nasal patency has been studied in healthy volunteers and in patients with vasomotor and allergic rhinitis. Both drugs applied topically increased nasal patency. The effect of a single dose of either compound lasted for several hours. Prostaglandin E1 produced nasal irritation and throbbing, lacrimation, headache and sore throat. Except for occasional brief nasal irritation, these side effects were not encountered with 17 phenyl trinor PGE2.     

Purified interferon as protection against rhinovirus infection.

In a double-blind placebo-controlled study a preparation of human leucocyte interferon purified by affinity chromatography using a monoclonal antibody and applied by repeated nasal sprays reduced the incidence and severity of colds in volunteers challenged with human rhinovirus 9. Although interferon itself caused some symptoms, these were minor compared with the clinical colds. Interferon activity was still detectable in nasal washings as long as 26 hours after the last dose in about half the volunteers on active treatment.     

Nasal obstruction as a cause of reduced PCO2 and disordered breathing during sleep

Nasal obstruction is a cause of disordered breathing during sleep. Our previous study demonstrated diminished end-tidal PCO2 with nose obstruction while subjects were awake. If this is also the cause during sleep, decreased CO2 stimulus may easily induce apnea, hypopnea, and disordered breathing. To test this hypothesis, six male volunteers were examined to compare sleep disorders during both nose-open and nose-obstructed conditions. End-tidal PCO2 during nose-obstructed sleep was lower than that during nose-open sleep in all of the subjects. Furthermore apnea during nasal obstruction occurred most frequently shortly after transition to a deeper sleep stage. These results suggest that diminished PCO2 stimulus combined with depressed behavioral activity play an important role for disordered breathing in nose-obstructed sleep.     

Effect of topical prostaglandins on nasal patency in man

The effect of prostaglandin E₁ and 17 phenyl trinor PGE₂ on nasal patency has been studied in healthy volunteers and in patients with vasomotor and allergic rhinitis. Both drugs applied topically increased nasal patency. The effect of a single dose of either compound lasted for several hours. Prostaglandin E₁ produced nasal irritation and throbbing, lacrimation, headache and sore throat. Except for occasional brief nasal irritation, these side effects were not encountered with 17 phenyl trinor PGE₂.     

Staphylococcus aureus nasal carriage is not associated with known polymorphism in the Vitamin D receptor gene

The vitamin D endocrine system has been shown to influence the immune response and polymorphisms in the vitamin D receptor (VDR) gene have been associated with susceptibility to infectious diseases. We determined if the Cdx2, FokI and BsmI-ApaI-TaqI polymorphisms in the VDR gene were associated with nasal carriage of Staphylococcal aureus. We defined the S. aureus nasal carriage status (persistent, intermittent or non-carriage) for a group of more that 2000 elderly volunteers. The prevalence of persistent S. aureus nasal carriage was 18%, which was, however, not associated with any of the variant VDR genotypes. Our study into genetic determinants of S. aureus carriage patterns is the largest in the field, but still we found no association between VDR gene variation and S. aureus nasal carriage.     

Downregulation of peroxisome proliferator-activated receptors (PPARs) in nasal polyposis

Background

Peroxisome proliferator-activated receptor (PPAR) α, βδ and γ are nuclear receptors activated by fatty acid metabolites. An anti-inflammatory role for these receptors in airway inflammation has been suggested.

Methods

Nasal biopsies were obtained from 10 healthy volunteers and 10 patients with symptomatic allergic rhinitis. Nasal polyps were obtained from 22 patients, before and after 4 weeks of local steroid treatment (fluticasone). Real-time RT-PCR was used for mRNA quantification and immunohistochemistry for protein localization and quantification.

Results

mRNA expression of PPARα, PPARβδ, PPARγ was found in all specimens. No differences in the expression of PPARs were obtained in nasal biopsies from patients with allergic rhinitis and healthy volunteers. Nasal polyps exhibited lower levels of PPARα and PPARγ than normal nasal mucosa and these levels were, for PPARγ, further reduced following steroid treatment. PPARγ immunoreactivity was detected in the epithelium, but also found in smooth muscle of blood vessels, glandular acini and inflammatory cells. Quantitative evaluation of the epithelial immunostaining revealed no differences between nasal biopsies from patients with allergic rhinitis and healthy volunteers. In polyps, the PPARγ immunoreactivity was lower than in nasal mucosa and further decreased after steroid treatment.

Conclusion

The down-regulation of PPARγ, in nasal polyposis but not in turbinates during symptomatic seasonal rhinitis, suggests that PPARγ might be of importance in long standing inflammations.     

Elevation of soluble interleukin-2 receptor levels in nasal allergy

To investigate soluble IL-2 receptor (sIL-2R) levels in nasal allergy, the sera and nasal secretions from patients with nasal allergy and from healthy subjects were subjected to a double-epitope enzyme-linked immunosorbent assay. Significant elevation of sIL-2R concentrations in the sera and nasal secretions was observed in the allergy patients (n = 26) compared with those of healthy subjects (n = 9). IL-2R-positive (CD25(+)) cells were observed in the crust formed in an allergic nasal mucosa. The concentration of sIL-2R in the sera correlated neither with the eosinophil count of the peripheral blood count nor with clinical severity. The concentration of sIL-2R in the nasal secretions was significantly higher compared with that in the sera from allergic patients (p < 0.01), whereas no significant difference was observed between sIL-2R levels in the sera and nasal sections from normal subjects. These findings indicate that sIL-2R plays an essential role in allergic processes by regulating IL-2R-positive cells recruited into the nasal mucosa.     

Production of Common Colds in Human Volunteers by Influenza C Virus

Influenza C virus was intranasally administered to volunteers; most were infected and nine developed symptoms of common cold.Increasing titres of serum haemagglutination-inhibiting antibody and complement-fixing antibody were detected. Virus neutralizing activity in nasal secretion was not correlated with either resistance to infection or the occurrence of overt illness. Interferon was detected in the nasal secretions of some subjects.     

A comparison of some pharmacological actions of prostaglandin E1, 6-oxo-PGE1 and PGI2

Some pharmacological actions of prostaglandin E1 (PGE1), 6-oxo-PGE1 and PGI2 have been studied. 6-oxo-PGE1 and PGE1 relaxed guinea-pig tracheal muscle in vitro and increased nasal patency in normal volunteers and in subjects with vasomotor rhinitis whereas PGI2 produced opposite effects. All three compounds produced bronchodilatation in the anaesthetised guinea-pig and relaxed human respiratory tract muscle in vitro. PGI2 was several times more potent than either 6-oxo-PGE1 or PGE1 against ADP-induced aggregation of human and baboon platelets in vitro. Intravenous 6-oxo-PGE1 in the baboon caused an ex vivo inhibition of platelet aggregation, but the EC50 was 7.7 times that of PGI2. As a vasodepressor in the baboon 6-oxo-PGE1 and PGI2 were equipotent. Thus with the exception of the vasodepressor effect, the actions of 6-oxo-PGE1 qualitatively and quantitatively resembled those of the structurally related PGE1 rather than those of PGI2.     

Effects of intravenous infusions of prostaglandin D2 in man

Prostaglandin D₂ (PGD₂) was infused intravenously into normal male volunteers. Seven subjects received infusions of 16, 32, 64 ng/kg/min and six of these a further dose of 128 ng/kg/min. Each individual's maximum dose was limited by discomfort caused by intense facial flushing and nasal congestion. At these doses there was no significant effect on systolic or diastolic blood pressure nor on spirometric measurements. There was a small but statistically significant tachycardia at 64 and 128 ng/kg/min. Collagen- and adenosine diphosphate (ADP)-induced platele aggregation was not affected at any of the infusion rates. Infused PGD₂ is unlikely to be a useful antithrombotic agent.     

Trigeminal chemosensitivity: Differences in relation to the time of the day

Day-night differences of trigeminal chemosensitivity were investigated in 18 healthy volunteers employing both pain-related cortical potentials and pain ratings in response to stimulation of the nasal mucosa with CO2. Day-night differences were found with N 1 P2 amplitudes, P2 latencies and pain ratings. It is concluded that the time of the day must not be ignored when human chemosensitivity is investigated at suprathreshold levels.      

Estimation of Respiratory Nasal Pressure and Flow Rate Signals Using Different Respiratory Sound Features

BackgroundRespiratory sounds are associated with the flow rate, nasal flow pressure, and physical characteristics of airways. In this study, we aimed to develop the flow rate and nasal flow pressure estimation models for the clinical application, and find out the optimal feature set for estimation to achieve the optimal model performance.MethodsRespiratory sounds and flow rate were acquired from nine healthy volunteers. Respiratory sounds and nasal flow pressure were acquired from twenty-three healthy volunteers. Four types of respiratory sound features were extracted for flow rate and nasal flow pressure estimation using different estimation models. Effects of estimations using these features were evaluated using Bland-Altman analysis, estimation error, and respiratory sound feature calculation time. Besides, expiratory and inspiratory phases divided estimation errors were compared with united estimation errors.ResultsThe personalized logarithm model was selected as the optimal flow rate estimation model. Respiratory nasal flow pressure estimation based on this model was also performed. For the four different respiratory sound features, there is no statistically significant difference in flow rate and pressure estimation errors. LogEnvelope was, therefore, chosen as the optimal feature because of the lowest computational cost. In addition, for any type of respiratory sound feature, no statistically significant difference was observed between divided and united estimation errors (flow rate and pressure).ConclusionRespiratory flow rate and nasal flow pressure can be estimated accurately using respiratory sound features. Expiratory and inspiratory phases united estimation using respiratory sounds is a more reasonable estimation method than divided estimation. LogEnvelope can be used for this united respiratory flow rate and nasal flow pressure estimation with minimum computational cost and acceptable estimation error.     

Expression and localization of the thromboxane A2 receptor in human nasal mucosa

Thromboxane A2 (TXA2) has been thought a potent mediator involved in allergic rhinitis, because TXA2 was recovered from the nasal lavage fluid of allergic rhinitis patients after allergen provocation and TXA2 receptor antagonists relief nasal allergic symptoms. In order to clarify the expression of TXA2 receptor in human nasal mucosa, we investigated TXA2 receptor mRNA expression and its protein localization by polymerase chain reaction (PCR) and immunohistochemistry, respectively. Human turbinates were obtained after turbinectomy from 10 patients with nasal obstruction refractory to medical therapy. RT-PCR analysis of total RNA from nasal mucosa demonstrated the expression of TXA2 receptor alpha mRNA. The immunohistochemical studies revealed that anti-TXA2 receptor alpha antibody labeled vascular smooth muscle cells, vascular endothelial cells, epithelial cells and submucosal glands in the nasal mucosa. The results may have an important clinical implication for understanding the role of TXA2 receptor on upper airway diseases such as allergic rhinitis and non-allergic rhinitis.     

Intranasal administration of alpha-human natriuretic peptide produces a prolonged diuresis in healthy man

The effects of an intranasal administration of synthetic alpha-human natriuretic polypeptide (alpha-hANP) were studied in 8 healthy male volunteers. They were given an intranasal administration of alpha-hANP at doses of 0.56-0.62 microgram/kg twice in the same day, the first and second administrations being separated by 180 min. Urine volume and urinary sodium excretion increased 2 to 3-fold 60 min after each administration. There were no significant changes in blood pressure, heart rate, glomerular filtration rate, plasma renin activity and plasma concentration of aldosterone, cortisol and catecholamines. The intranasal administration of alpha-hANP was well tolerated by the volunteers, and no untoward effect was observed. The results suggest that alpha-hANP can be used as a nasal spray in patients with overhydration.     

Ambient oxygen regulates epithelial metabolism and nitric oxide production in the human nose.

The effects of ambient O(2) tension on epithelial metabolism and nitric oxide (NO) production (VNO) in the nasal airway were examined in nine healthy volunteers. Nasal VNO, O(2) consumption (VO(2)), and CO(2) production (VCO(2)) were measured during normoxia followed by gradual hypoxia from 21 to 0% O(2) concentration. Nasal VO(2), VCO(2), and respiratory quotient during normoxia were determined to be 1.19 +/- 0.04 ml/min, 1.60 +/- 0.04 ml/min, and 1.35 +/- 0.04, respectively. Hypoxia exposure to the nasal cavity significantly decreased both VCO(2) and VNO [VCO(2): 1.60 +/- 0.04 to 0.96 +/- 0.03 ml/min (P < 0.01), VNO: 530 +/- 15 to 336 +/- 9 nl/min (P < 0.01)]. VNO was reduced commensurately with gradual decline in O(2) tension, and the apparent K(m) value for O(2) was determined to be 23.0 microM. These results indicate that the nasal epithelial cells exchange O(2) and CO(2) with ambient air in the course of their metabolism and that nasal epithelial cells can synthesize NO by using ambient O(2) as a substrate. We conclude that air-borne O(2) diffuses into the epithelium where it may be utilized for either cell metabolism or NO synthesis.     

Nasal secretions of Neisseria lactamica carriers have an inhibitory effect on Neisseria meningitidis attachment to human oroepithelial cells

Nasal secretions of volunteers colonized by N. lactamica impaired the attachment of N. lactamica and of meningococci of groups A and B to oroepithelial cells. Bacterial adherence was found to be mediated by nonpiliated adhesins with antigen(s) which probably are shared by the strains tested. Although a strong attachment-inhibiting activity arises in their nasal secretions, volunteers remained colonized by N. lactamica. This evidence suggest that the eradication of Neisseria carriage is a multifactorial event.     

LMR spectroscopy: a new sensitive method for on-line recording of nitric oxide in breath.

Laser magnetic resonance spectroscopy (LMRS) is a sensitive and isotope-selective technique for determining low concentrations of gaseous free radicals with high time resolution. We used this technique to analyze the nitric oxide (NO) concentration profile while simultaneously measuring the flow and expired volume during several single breathing cycles. Eight healthy, nonallergic volunteers were investigated. An initial NO peak was found in all breathing cycles before the NO concentration dropped to a relatively stable plateau in the late phase of expiration. The nasal NO peak was significantly higher than the oral NO peak. The nasal NO plateau was always higher than the oral NO plateau. The height of the initial nasal and oral NO peak rose with increasing duration of breath hold, whereas the late expiratory NO plateau changed only little for either the nasal or the oral breathing cycles. Our findings demonstrate, in line with other reports using other techniques, that the nose is the primary source for NO within the airways.     

Recovery of nasal prostaglandin production after inhibition by aspirin

We have investigated the duration of the inhibitory effects of aspirin in eight healthy volunteers after oral administration of a single 500 mg dose. Prostaglandin E2, D2 and leukotriene C4 levels in nasal lavage fluid were measured by radioimmunoassay without purification by high performance liquid chromatography. The inhibitory effects of aspirin on eicosanoid synthesis were maximum between 1 h to 24 h, showing total recovery within 3-5 days. LTC4 synthesis was not modified by aspirin.     

Expression of prostaglandin D synthase and the prostaglandin D2 receptors DP and CRTH2 in human nasal mucosa

BACKGROUND: Prostaglandin D2 (PGD2) is released from mast cells during the allergic response. OBJECTIVE: Since PGD2 has been shown to induce nasal congestion in humans, we investigated the distribution of hematopoietic prostaglandin D synthase (PGDS) and the two PGD2 receptors, DP and CRTH2 in human nasal mucosa from healthy subjects and subjects suffering from polyposis, a severe form of chronic rhinosinusitis. METHODS: DP mRNA expression was detected by in situ hybridization while PGDS, CRTH2 and various leukocyte markers expression were revealed by immunohistochemistry. RESULTS: In the normal mucosa, PGDS was only detected in few resident mast cells while CRTH2 was undetectable. In contrast, DP receptor mRNA was detected in epithelial goblet cells, serous glands and in the vasculature. In the nasal mucosa of subjects suffering from polyposis: (1) PGDS was detected in mast cells and other large infiltrating inflammatory cells, (2) both DP mRNA and CRTH2 were detected in eosinophils and (3) CRTH2 was detected on a subset of infiltrating T cells. Although DP mRNA could not be detected in the T cells invading the nasal mucosa, it was found to be expressed in the T cells present in the lymph node and the thymus from normal individuals. CONCLUSION: This study indicates that cells capable of producing PGD2 are present in the nasal mucosa and that both PGD2 receptors, DP and CRTH2, might play a role in inflammatory disease of the upper airways.