Documentation of the nasal nitric oxide response to humming: methods evaluation.

RATIONALE: Nitric oxide (NO) is present at higher concentrations in the nasal cavity than in the lower airway, and at even higher concentrations within the paranasal sinuses proper. When the paranasal sinus ostia are patent, acoustic activity produced by vocalization with closed lips (humming) promotes mixing of sinus with nasal gases, producing a further increase in nasal NO. We wished to evaluate procedures for the documentation of the nasal NO response to humming. MATERIALS AND METHODS: We compared two ATS-recommended sampling methods: 1) active exhalation of lower airway gas (parallel technique) and 2) passive aspiration of nasal gas with closed velopharynx (series technique). Variables controlled for included sampling rate, external resistance (parallel method), humming frequency, humming duration, and intertrial interval. Prior to upper airway sampling, exhaled lower airway NO was determined utilizing ATS-standardized technique. RESULTS: Ten volunteers (seven males and three females, aged 21-58) with no history of respiratory allergies or sino-nasal disease were studied in a single session each. The parallel technique documented an increase in nasal NO during the humming manoeuvre in all subjects (mean ratio of humming-to-quiet NO, 4.2), whereas the series technique did so in eight of 10 subjects (mean ratio 2.1). Correcting for admixture from the lower airway, the ratio of humming-to-quiet NO was greater with the parallel than series sampling technique (P < 0.05). CONCLUSIONS: Documentation of the response of nasal NO to humming in subjects without sino-nasal disease was consistently achievable by parallel sampling using commercially available equipment. Specific operational procedures are proposed.

Acute respiratory responses of the mouse to chlorine.

In human subjects 15-min exposure to 0.5-1.0 ppm chlorine gas causes a nasal obstructive response in the absence of a marked sensation of irritation. The current investigation was designed to assess the response of the mouse for comparative purposes. Respiratory physiological responses were measured in female C57Bl/6J mice exposed to 0.8 to 4.0 ppm chlorine gas. Chlorine was a potent sensory irritant with an RD50 of 2.3 ppm. The gas produced airway obstruction as indicated by a concentration-dependent increase in specific airways resistance (sRaw) during the 15-min exposure. At 0.8 ppm, chlorine produced only mild sensory irritation (<20% change in breathing frequency) and a 65% increase in sRaw. Pretreatment with atropine was without effect on the obstructive response, suggesting a lack of involvement of muscarinic cholinergic pathways. Pretreatment with the sensory nerve toxin, capsaicin, dramatically reduced both the sensory irritation and obstructive responses to chlorine, suggesting the involvement of sensory nerves. Studies were also performed using the surgically isolated upper respiratory tract of the anesthetized mouse. Chlorine was efficiently scrubbed from the airstream (>97%) in that site and produced an obstructive response that was of sufficient magnitude to account for the entire response observed in the intact animal. In summary, chlorine gas produces an immediate nasal obstructive response in the mouse that appears to be similar to that in the human.

Work-related asthma and latex allergy. Sorting out the types, causes, and consequences.

Work-related asthma now has clear definitions based on criteria agreed upon by the American College of Chest Physicians. The clinician should suspect occupational asthma, irritant-induced asthma, or work-aggravated asthma in adults with new-onset asthma or asthma symptoms that worsen during work, after work (late allergic response), or over the course of workdays. The possible cause should be sought, and a skin test or immunoassay should be performed, if possible,to he;lp detect sensation. Workup als o includes objective documentation of worsening of symptoms and airway obstruction during occupational exposure. If this information is inconclusive, an inhalation challenge may be considered. Medical management is the same as for nonoccupational asthma, but cessation of exposure to the specific agent is necessary to improve long-term diagnosis. Latex allergy and latex-induced asthma are becoming more common in the workplace, particularly in the healthcare field. No commercially available standard serum or skin test are available for diagnosis. The principal treatment is avoidance of latex, which can be achieved in most cases without extensive changes to the workplace.

Chest wall pain and possible rhabdomyolysis after chloropicrin exposure. A case series.

Three cases are summarized in which persistent chest wall pain, as well as elevations of creatine phosphokinase (CK) levels, occurred after exposure to chloropicrin vapor in an agricultural chemicals facility. Both the severity of the symptoms and the degree of biochemical abnormality appeared to follow a dose-response relationship. Myoglobinuria, on the other hand, was not found. Elevation of CK after chloropicrin exposure has not previously been reported and may represent low-grade rhabdomyolysis. Workups performed after symptomatic chloropicrine exposure should include CK-level determination.

Interobserver variability in the interpretation of unenhanced helical CT for the diagnosis of ureteral stone disease.

PURPOSE: The purpose of this study was to analyze interobserver agreement in the interpretation of unenhanced helical CT (UHCT) for the evaluation of ureteral stone disease and obstruction. METHOD: One hundred three UHCT examinations were independently and retrospectively reviewed by five readers including attending radiologists, a radiology resident, and an attending urologist. Examinations were interpreted as positive, negative, or indeterminate for ureteral stone disease and obstruction. The Cohen kappa test was used to measure interobserver agreement. The accuracy of the readers was also assessed. RESULTS: The kappa value ranged from 0.67 to 0.71 among the three attending radiologists and from 0.65 to 0.67 among the radiology attending physicians and radiology resident. Although the urologist tended to agree less well with the other readers (kappa range: 0.33-0.46), there was no statistically significant difference (p < 0.05) in the accuracy among all five readers. The percentage of cases interpreted as indeterminate ranged from 8 to 25% and almost invariably involved difficulty distinguishing phleboliths from minimally obstructing distal ureteral calculi. The percentage of UHCT scans correctly interpreted as positive and correctly interpreted as negative ranged from 73% (n = 27) to 86% (n = 32) and 63% (n = 22) to 86% (n = 30), respectively. CONCLUSION: Interobserver agreement was very good among the radiology attending physicians and resident and moderate with the urologist. The examination is an accurate technique in the evaluation of ureteral stone disease, although limitations exist, particularly in the diagnosis of minimally obstructing distal ureteral calculi.

Subjects with seasonal allergic rhinitis and nonrhinitic subjects react differentially to nasal provocation with chlorine gas.

BACKGROUND: Nasal irritation and associated symptoms (nasal congestion, rhinorrhea, and sinus headache) are important elements of the response to indoor and outdoor air pollution. Marked interindividual variability in such symptoms has been suggested clinically and epidemiologically, but little experimental data exist on this issue. OBJECTIVE: We sought to test the hypothesis that subjects with seasonal allergic rhinitis (SAR) exhibit a more marked physiologic response (congestion) after nasal irritant provocation than do nonrhinitic subjects. METHODS: We studied eight subjects with SAR and eight nonrhinitic subjects; subjects with SAR were studied out of season. In a single-blind crossover study, subjects had their nasal airway resistance (NAR) measured in triplicate before, immediately after, and 15 minutes after a 15-minute exposure to either filtered air or 0.5 ppm chlorine in filtered air, administered through a nasal mask in a climate-controlled chamber. Log-transformed NAR values were analyzed in a repeated-measures analysis of variance model, with confirmatory testing using paired t tests. RESULTS: The net (chlorine minus air day) percent change in NAR from baseline (before exposure) to immediately after exposure was +24% in the SAR group and +3% in the nonrhinitic group (p < 0.05). The corresponding net changes from baseline to 15 minutes after exposure were +21% in the SAR group and -1% in the nonrhinitic group (p < 0.05). CONCLUSIONS: The observed augmented nasal congestive response of subjects with SAR versus nonrhinitic subjects to a controlled low-level chemical irritant provocation is consistent with epidemiologic surveys showing a higher prevalence of nasal symptoms among subjects with SAR than nonrhinitic subjects in environments involving irritant air pollutants.

A comparison of two methods for determining nasal irritant sensitivity.

Nasal irritation and irritant-induced reflexes (rhinorrhea and congestion) are prominent symptoms associated with indoor and ambient air pollution, and marked heterogeneity in individual sensitivity has been suggested. Nevertheless, there is currently no generally accepted functional index of nasal irritant sensitivity available for clinical use. To address this issue, we compared two objective measures of nasal irritant sensitivity: a CO2 detection task, and CO2-induced transient disruption of respiratory pattern (pulsed CO2 acting as an odorless irritant). Using a respiratory flow thermocouple to produce a continuous recording of respiratory pattern, we challenged 20 normal adult volunteers (13 males and 7 females, average age 39.4 years) with brief (approximately 3 second) pulses of the odorless irritant carbon dioxide. Increasing levels of CO2 (10-70%, vol/vol), paired with filtered air in random order, were presented unilaterally by nasal cannula of fixed geometry, synchronized with the inspiratory phase of the respiratory cycle. All subjects yielded CO2 detection thresholds, whereas within the constraints of the testing method (subjective irritation rating < or = "very strong"), only 13 of 20 subjects (65%) exhibited transient disruption of their breathing pattern. Further, although decreased respiratory volume (indirectly measured) appeared to be a common feature, several distinct patterns of respiratory alteration were observed, rendering objective scoring more difficult. Finally, some subjects showed CO2-induced respiratory disruption intermittently from trial to trial, implying that rapid adaptation occurs. Determination of the CO2 detection threshold therefore appears to be the more objective and consistently applicable endpoint for determining individual nasal irritant sensitivity.

Dose-response assessment of airborne methyl isothiocyanate (MITC) following a metam sodium spill.

A tank car derailment in northern California in 1991 spilled metam sodium into the Sacramento River, and released its breakdown product, methyl isothiocyanate (MITC), into the air. This paper describes the risk evaluation process used. Over 240 individuals reported symptoms such as eye and throat irritation, dizziness, and shortness of breath. Reference exposure levels (RELs) for 1 hr were developed for MITC and compared to exposure concentrations. Ocular irritation in cats was the most sensitive endpoint reported. The no observed adverse effect level (NOAEL), divided by an uncertainty factor (UF) of 100, produced an REL of 0.5 ppb of MITC in air to prevent discomfort. An REL to prevent disability was estimated to be 40 ppb. An REL to prevent life-threatening injury was estimated to be 150 ppb. Measured MITC levels ranged from 0.2-37 ppb and estimated peak levels ranged from 140-1600 ppb. The usefulness of RELs for emergency planning is discussed.

Polymer fume fever and other fluorocarbon pyrolysis-related syndromes.

Polymer fume fever usually occurs as a self-limited systemic illness with only minor pulmonary symptoms. Like metal fume fever, constitutional signs and symptoms typically present several hours after initial exposure, often giving rise to a misdiagnosis of viral "flu." Compared to metal fume fever, polymer fume fever has a more varied clinical presentation, the severity of which depends upon the specific conditions of exposure. When higher temperatures and/or longer durations of exposure are involved, significant pulmonary involvement, including radiographic consolidation, is a potential complication. Although a number of industrial outbreaks have implicated the smoking of contaminated cigarettes as a vehicle of exposure, any industrial or household activity in which PTFE is heated above 350-400 degrees C puts nearby workers or residents at risk of illness and is to be avoided without strict industrial hygiene controls.

Clinical smoke inhalation injury: systemic effects.

Exposure to asphyxiant gases is a ubiquitous feature of the fire environment, particularly in structural (or closed-space) fires. The clinician evaluating the smoke-inhalation patient must keep in mind the manifold actions of systemic toxicants upon an individual whose pulmonary gas exchange may be compromised and whose circulatory and metabolic status may be stressed by burns, hypo- or hypervolemia, and intercurrent disease. Also to be considered is the likelihood of exposure to multiple toxicants whose physiologic effects may be synergistic and whose therapeutic demands may be conflicting. As newer therapeutic regimens and rapid laboratory tests become available, the clinician should be prepared to evaluate their strengths and limitations for the complex task of evaluating and treating smoke-inhalation patients.

Mixing incompatibilities and toxic exposures.

A number of consumer and commercial products may react, upon inappropriate mixing, to produce substances of greater toxicity than the starting materials. Consumer product mixing incompatibilities have been well documented and warning labels appear on high-risk products. In industry, a wider array of potential mixing incompatibilities exists and includes potential accidents in chemical storage and hazardous material handling. Emergency response personnel are a group who often deal with inadvertent mixing related to transportation and other hazardous materials incidents. This article assembles some better-known examples of toxicologically significant exposures resulting from inadvertent or deliberate mixing of incompatible materials.

Occupational and environmental disorders of the special senses.

Occupational hazards to vision, hearing, balance, olfaction, and taste typically constitute a small fraction of specialty medical practices in ophthalmology and otolaryngology. With the possible exception of noise-related hearing loss and VDT eye hazards, the scientific literature regarding these hazards tends to be scattered and variably accessible to occupational medicine practitioners. It is hoped that the current review will heighten the appreciation of these hazards among both generalists and specialists, and will encourage future documentation and reporting of this interesting group of disorders.

Prevention of psychological disability after occupational respiratory exposures.

"Psychological injury" in the workplace constitutes the fastest-growing sector of workers' compensation disability claims in several states. Most such claims pertain to effects of "occupational stress," including interpersonal conflicts with supervisors or co-workers, adaptation to changing work practices, and job insecurity. Of equal interest are the psychological consequences of chemical insults on the job. In the case of occupational respiratory exposures, psychological co-morbidity may occur along with a variety of acute, chronic, and latent illness states. Both predictable responses (such as adjustment reactions to disabling physical conditions) and idiopathic patterns (such as the development of odor-conditioned panic attacks or panic disorder) have been described. Physicians who evaluate and treat such patients need to be alert to the potential interaction of physiological and psychological stressors. Effective prevention and treatment requires not only an appreciation of the patient's view of the disease process, but also a recognition of the role of prognostic uncertainty in the subsequent development of anxiety symptoms. In some cases, exclusive attention to physical signs and symptoms may actually lead to a worsening of impairment and disability.