Respiratory function in healthy ever-smokers is impaired by smoking habits in a dose-dependent manner.

BACKGROUND: There is limited information about the respiratory function of ever-smokers without lung disorders. We sought to assess the effects of smoking habits on respiratory function in subjects without lung disorders. METHODS: Subjects were recruited from among patients without any evidence of respiratory disorders who visited rural primary care clinics. Each participant was asked to answer a questionnaire that included questions smoking history. Their forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were measured. RESULTS: We analyzed 802 subjects (364 men and 438 women). The means of the lambda-mu-sigma method derived z-score of FEV1 (zFEV1) both in current-smokers and ex-smokers were lower than that in never-smokers. The mean zFEV1 in the ever-smokers with more than 30 pack-years of smoking history were lower than that in the ever-smokers with less smoking history. Univariate analysis showed that there were significant negative correlations between pack-years and zFEV1 both in the ex-smokers and current-smokers. There was no significant correlation between the duration of smoking cessation and zFEV1 in the ex-smokers. CONCLUSIONS: Our data suggests that respiratory function in healthy ever-smokers is decreased based on smoking habits in a dose-dependent manner. Even after a long period of smoking cessation, the decreased respiratory function seems to be maintained in ex-smokers.

[The add-on effect of omalizumab on patients with uncontrolled bronchial asthma].

A high-dose administration of inhaled corticosteroid is effective in the majority of patients with bronchial asthma, but is often difficult to attain sufficient control in certain subsets of patients. Omalizumab has recently emerged as a promising drug for bronchial asthma. To assess its add-on effect we administered omalizumab to patients with uncontrolled atopic asthma for more than 16 weeks and gave them questionnaires. The study population comprised 9 patients with frequent asthmatic symptoms despite the administration of high-dose inhaled corticosteroid and other disease controllers. We scored disease control using the Asthma Health Questionnaire-33-Japan and the Asthma Control Test, and evaluated the frequencies of short-acting beta2-agonist use for rescue and drip infusion of theophyllines and/or systemic steroids in a retrospective fashion. Asthmatic scores were significantly improved after 16 weeks of omalizumab therapy. The frequencies of reliever use and drip infusion were also decreased. These trends were present even in patients in whom no aeroallergen-specific IgE antibodies were detected. No statistically significant side effects were observed. Our study confirmed the add-on effect of omalizumab based on evaluation by simple questionnaires. Further studies are needed to clarify whether omalizumab therapy is suitable for patients without specific IgE antibodies.

[Comparison between predicted equations obtained by standard Japanese values and present predicted equations for vital capacity and forced expiratory volume in one second].

Until recently, predicted values of vital capacity (VC) and forced expiratory volume in one second (FEV1) have been calculated with Baldwin's equation (VC-B) and Berglund's equation (FEV1-B) respectively, in Japan. Due to several problems using these equations, new prediction equations of VC (VC-J) and FEV1 (FEV1-J), which were created using data from healthy Japanese, were provided by the Japanese Respiratory Society in 2001. In the present study, we studied the validity of these prediction equations. Also, we compared the outcomes of patients who match respiratory handicap "indexes" with VC-B and VC-J. The subjects were all adult patients whose respiratory function was tested in Asahikawa Medical College Hospital between 1998 and 2006. Cases which were diagnosed as contractive respiratory disorder increased approximately 2-fold when %VC was calculated with VC-J compared with VC-B. Grade 4 or higher respiratory handicap scores increased 20% if the index was calculated with VC-J compared with VC-B. There was no significant difference in mortality between the respiratory handicap grade 3 scores calculated with VC-J and VC-B. Also, there was no significant difference in mortality between grade 4 respiratory handicap scores calculated with VC-J and VC-B. These findings suggest that the prediction equations using Japanese data increase the number of predicted respiratory disorders, and those additional cases have the same prognoses as those cases diagnosed with the former criteria.

Aging increases upper airway collapsibility in Fischer 344 rats.

The upper airway muscles play an important role in maintaining upper airway collapsibility, and the incidence of sleep-disordered breathing increases with age. We hypothesize that the increase in airway collapsibility with increasing age can be linked to changes in upper airway muscle mechanics and structure. Eight young (Y: 6 mo) and eight old (O: 30 mo) Fischer 344 rats were anesthetized and mechanically ventilated, and the pharyngeal pressure associated with flow limitation (Pcrit) was measured 1) with the hypoglossal (cnXII) nerve intact, 2) following bilateral cnXII denervation, and 3) during cnXII stimulation. With the cnXII intact, the upper airways of older rats were more collapsible compared with their younger counterparts [Pcrit = -7.1 +/- 0.6 (SE) vs. -9.5 +/- 0.7 cmH2O, respectively; P = 0.033]. CnXII denervation resulted in an increase in Pcrit such that Pcrit became similar in both groups (O: -4.2 +/- 0.5 cmH2O; Y: -5.4 +/- 0.5 cmH2O). In all rats, cnXII stimulation decreased Pcrit (less collapsible) in both groups (O: -11.3 +/- 1.0 cmH2O; Y: -10.2 +/- 1.0 cmH2O). The myosin heavy chain composition of the genioglossus muscle demonstrated a decrease in the percentage of the IIb isoform (38.3 +/- 2.5 vs. 21.7 +/- 1.7%; P < 0.001); in contrast, the sternohyoid muscle demonstrated an increase in the percentage of the IIb isoform (72.2 +/- 2.5 vs. 58.4 +/- 2.3%; P = 0.001) with age. We conclude that the upper airway becomes more collapsible with age and that the increase in upper airway collapsibility with age is likely related to altered neural control rather than to primary alterations in upper airway muscle structure and function.

Renal abscess with Morganella morganii complicating leukemoid reaction.

We report a case of leukemoid reaction (LR) complicating renal abscess caused by Morganella morganii infection in an 80-year-old man. On administration, laboratory tests revealed white blood cell count of 76160 /microL and C reactive protein 3.09 mg/dL. Although chronic myeloid leukemia was suspected, bcr/abl fusion transcript was not observed. Contrast enhanced computer tomography imaging of the abdomen showed abscess in the right kidney. M. morganii was detected repeatedly in material of liquid from the abscess and arterial blood culture. To our knowledge, this is the first case of M. morganii infection complicating LR.

Intermittent hypoxia reduces upper airway stability in lean but not obese Zucker rats.

Obstructive sleep apnea involves intermittent periods of airway occlusions that lead to repetitive oxygen desaturations. Exposure to chronic intermittent hypoxia (IH) in rats increases diurnal blood pressure and alters skeletal muscle physiology. The impact of IH on upper airway muscle function is unknown. We hypothesize that IH exposure increases upper airway collapsibility in rats due to alterations of the muscles surrounding the upper airway. Lean and obese rats were exposed to cyclic alterations in O(2) levels (20.6%-5%) every 90 s, 8 h/day for 6 days/wk for 12 wk. Following the exposure period, arterial pressure was recorded via the tail artery in conscious unrestrained rats. Mean arterial pressure was increased in lean IH but not in obese IH-exposed Zucker rats (P < 0.05). The pharyngeal pressure associated with airway collapse (P(crit)) was measured under anesthesia during baseline conditions and then during supramaximal stimulation of the hypoglossal nerve (cnXII). Baseline P(crit) was more positive (more collapsible) in lean but not obese rats following 12 wk of IH (P < 0.05), while supramaximal stimulation of cnXII increased airway stability (decreased P(crit)) in both lean and obese Zucker rats following IH to levels that were similar to their respective room air controls. The in vitro peak tension and the expression of the individual myosin heavy chain isoforms from the upper airway muscles were unaltered following IH. We conclude that IH leads to increases in baseline collapsibility in lean Zucker rats exposed to IH by nonmyogenic mechanisms.

Systemic administration of serotonin 2A/2C agonist improves upper airway stability in Zucker rats.

The effects of [+/-]-2,5-dimethoxy-4-iodoaminophentamine, a serotonin(2A/2C) receptor agonist, on pharyngeal airflow mechanics were examined in isoflurane-anesthetized lean and obese Zucker rats. The pharyngeal pressure associated with flow limitation, maximum inspiratory flow, oronasal resistance, genioglossus muscle activity, and arterial blood pressure (BP) were measured before and after the intravenous administration of the agonist. A robust activation of the genioglossus muscle in all lean and obese rats was associated with decreased upper airway (UA) collapsibility (p < 0.05), unchanged maximum flow, and increased oronasal resistance (p < 0.05) in both groups. The changes in UA mechanics and BP after the drug were similar in lean and obese rats. The serotonin agonist had no effect on UA mechanics in a group of paralyzed (pancuronium bromide) rats, despite similar elevations in BP. There was a smaller decrease (p < 0.05) in UA collapsibility that was also associated with increased upstream resistance when the drug was administered after bilateral hypoglossal nerve transection. We conclude that systemic administration of a serotonin(2A/2C) receptor agonist improves UA collapsibility predominantly, but not exclusively, via stimulation of the hypoglossal nerves and also increases upstream resistance, at least in part, through activation of nonhypoglossal motoneuronal pools innervating the UA muscles.

[Symptoms in asthmatics living in cold districts during winter].

Exposure to cold is known as a potential exacerbating factor in asthmatics. However, few studies have investigated severity of symptoms during daily life in winter for asthmatics living in northern Hokkaido, the coldest region in Japan. We sent questionnaires to 126 asthmatics living in northern Hokkaido, and obtained answers from 116 patients (52 males, 64 females). Breathing difficulties during cold-air exposure were reported by 62.1% of patients. Furthermore, 19.6% of patients had experienced the need for bronchodilators following cold-air-induced attacks. Limitations to daily life in winter caused by exacerbated asthmatic symptoms were recognized by 48.3% of patients. Asthmatic exacerbation was experienced by 30% of patients in summer (May to August), compared to >35% in winter (September to April). No significant differences in results were noted between atopic and non-atopic patients. Improvements in respiratory symptoms during winter are thus necessary for better quality of life in asthmatics living in cold districts.

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.