Bronchial hyper-responsiveness: a technical update.

BACKGROUND: Bronchial hyper-responsiveness (BHR) is often regarded as a 'hallmark' of asthma, and bronchoprovocation testing is frequently performed to support a diagnosis of asthma. The European Respiratory Society (ERS) and American Thoracic Society (ATS) have recently updated their technical standards and guidelines for performing methacholine challenge testing (MCT), the most commonly performed clinical test of BHR. AIMS: To review the updated guidelines and discuss the various changes and their potential impact on clinicians. METHODS: We performed a systematic review of references identified using Medline and hand searches of identified articles. RESULTS: The new ERS and ATS guidelines recommend that MCT be performed using tidal breathing, not deep inspirations with breath holding, that results be reported as the PD20 (cumulative dose causing a 20% fall in forced expiratory volume in 1 s [FEV1]), rather than PC20 (concentration causing a 20% fall in FEV1), and that manufacturers of nebulizers and other delivery systems provide performance characteristics to allow calculation of PD20 values. Our preliminary survey found that the new guidelines are only slowly being adopted. CONCLUSIONS: Clinicians should be aware that recommended BHR testing methods, particularly for MCT, have changed. As a result, they should anticipate that test outcomes will increasingly be reported in terms of PD20, which will facilitate longitudinal assessment of their patients. Compliance with the new guidelines will increase the sensitivity of MCT in mild and asymptomatic asthmatics.

Bronchial hyperresponsiveness.

BACKGROUND: Bronchial hyperresponsiveness (BHR) is often regarded as a 'hallmark' of asthma and bronchoprovocation testing is frequently performed to support a diagnosis of asthma. However, BHR is also found in a spectrum of other lung diseases and can be provoked by a variety of specific stimuli. AIMS: To review the pathophysiology of BHR, discuss various methods of testing for BHR and describe the epidemiology of BHR in a variety of previously studied populations. METHODS: We performed a systematic review of references identified using Medline and hand searches of identified articles. Because of space limitations, we have included those reports that seem most representative of the overall BHR literature. RESULTS: BHR can be induced by a variety of stimuli that trigger a number of different but overlapping physiological mechanisms. Bronchoprovocation testing can be performed using a variety of stimuli, various protocols and differing test criteria, yielding results that may be discordant. Elevated rates of BHR have been reported in studies of smokers, chronic obstructive pulmonary disease patients, atopics, athletes, exposed workers and the general population. CONCLUSIONS: Due to the prevalence of BHR in a spectrum of clinical patients and working populations, clinicians should be aware that BHR is not specific for asthma. When performed correctly, the greatest clinical value of BHR testing is to rule out suspected asthma in patients in whom testing is negative. Assessment of BHR also provides insights into the pathological mechanisms of airway disease.

Is diacetyl a respiratory sensitizer? A reconsideration using QSAR, QMM, and competition experiments.

Concerns have been raised that diacetyl (DA) might be a respiratory sensitizer based on its LUMO energy similar to that of the respiratory allergen toluene-2,4-diisocyanate (TDI) and results of a local lymph node assay (LLNA) that reported an EC3 of 1.9%. To better understand the concerns, we performed a systematic literature review and experimental competition reactions between DA and TDI. The experimental evidence demonstrates that DA is at least 400-fold less reactive than TDI. The literature review finds evidence that the EC3 for DA is actually >11%. We conclude that DA is unlikely to have significant respiratory sensitization potential.

Application of PET deprotection for orthogonal photocontrol of aqueous solution viscosity.

Photorelease and photoisomerization of trans-cinnamic acid in aqueous CTAB solutions induces a bulk solution viscosity increase and decrease, respectively, triggered by orthogonal irradiation wavelengths.

Ketocoumarin dyes as electron mediators for visible light induced carboxylate photorelease.

Photoinduced mediated electron transfer to N-alkylpicolinium(NAP)-based esters has previously been shown to induce release of carboxylate anions. In this mechanism, electrons are shuttled between a good electron donor through a sensitizer/mediator to the NAP group which subsequently induces C-O bond cleavage. Previous studies have used UV-absorbing mediators to initiate substrate release with high photorelease efficiencies, but require long irradiation periods for quantitative deprotection. The current study improves upon previous systems by using lower energy visible light absorbing mediators that induce substrate release over shorter irradiation periods (i.e. higher overall photolytic efficacies).

A new photolabile protecting group for release of carboxylic acids by visible-light-induced direct and mediated electron transfer.

A new aqueous-compatible photoinduced electron transfer based photolabile protecting group has been developed for the release of carboxylic acids. The reduction potential of this group is more positive than previous systems, thereby allowing the use of sensitizers with modest oxidation potentials. Release of several carboxylic acids has been demonstrated using tris(bipyridyl)ruthenium(II) as both a direct sensitizer and a mediator for electron transfer between a good donor and the protecting group.

Photorelease of carboxylic acids mediated by visible-light-absorbing gold-nanoparticles.

Visible-light-absorbing citrate-stabilized gold nanoparticles and tryptophan-dithiane-conjugate-stabilized gold nanoparticles have been used to mediate electron transfer between dithiothreitol (DTT), a good electron donor, and an N-methylpicolinium ester in aqueous solution. Quantitative yield of the free carboxylate has been obtained with quantum yields of release, Phirel, ranging from 0.5 to 4.5.

Sources of interference in field studies of diesel exhaust emissions.

This article describes interferences encountered in a variety of occupational settings during industrial hygiene surveys of diesel particulate material (DPM) using the NIOSH 5040 Method. The method yields time-weighted-average measurements of elemental carbon (EC), organic carbon (OC), and total carbon (TC = EC + OC). NIOSH recommends EC as proxy for DPM, but other agencies (e.g., MSHA) regulate exposure as TC. Surveys were conducted in an engine factory and a wood treatment plant where diesel equipment was used, and in a foundry where its use was being considered. Full shift samples were collected using open-faced cassettes and cyclones fitted with 37-mm quartz fiber filters analyzed by the NIOSH 5040 Method. Non-DPM-related interferences were noted for both the OC and EC. In the engine factory and wood treatment facility, OC measurements were very high (range of 10.0-1600 microg/m(3)), while EC levels were mostly below the LOD. These findings almost certainly reflect interferences by cutting oil mists and airborne creosote respectively. In the foundry, EC levels were high and comprised mainly of larger (>4 microm) particles (open face samples: arithmetic mean = 136 microg/m(3), geometric mean = 74.0 microg/m(3); cyclone samples: arithmetic mean = 30.2 microg/m(3), geometric mean = 14.7 microg/m(3)). These findings suggest that OC interferences should be suspected if the EC:TC ratio is <0.35 and, if DPM surveys are performed with open-faced samplers, at least a small number of size-selective samplers should be employed to assure that results do not reflect EC interference by larger (i.e., >1-4 microm) particles. They also support the ACGIH decision to modify its proposed DPM TLV to specifically consider elemental carbon, rather than total carbon.

Comparison of NIOSH 5040 method versus Aethalometer to monitor diesel particulate in school buses and at work sites.

This study, undertaken initially to understand apparent differences between two recent reports of diesel particulate matter (DPM) inside school buses, involved side-by-side comparisons of two different methods for measuring ambient and occupational exposures to DPM. The NIOSH 5040 method yields time-weighted-average measurements of elemental carbon (EC) and organic carbon (OC), whereas the Aethalometer yields near-real time measures of carbonaceous particles (black carbon or BC) by optical absorption. The two methods were compared on three school buses and in three different work sites. Three side-by-side sampling configurations were used (open-faced filter with and without two different cyclones) in triplicate along with two or three Aethalometers. BC readings were correlated with results from open-faced cassettes, but there were statistically significant differences between the results of side-by-side Aethalometers. In addition, Aethalometer airflow rates were inaccurate, the instruments were sensitive to vibration, optical calibration could not be performed, and historically derived conversion factors to relate EC and BC were not appropriate. The Aethalometer could prove useful for monitoring of industrial work sites, but only after a method for external calibration and improvements in pump design and vibration isolation are developed.

Observations on the suitability of the aethalometer for vehicular and workplace monitoring.

A field study was undertaken to evaluate the suitability of the aethalometer, an instrument capable of performing near-real-time measurement of low-level (10-1,000 ng/m3) airborne combustion products, for vehicular and workplace monitoring. Several technical limitations were identified: (1) there was no ready means for external calibration of optical measurements; (2) airflow rates were unstable; (3) effective range of concentrations was limited; and (4) the aethalometer demonstrated sensitivity to movement and vibration. Unless addressed, these limitations will restrict future uses of the aethalometer for vehicular and workplace monitoring.

Exposure of miners to diesel exhaust particulates in underground nonmetal mines.

A study was initiated to examine worker exposures in seven underground nonmetal mines and to examine the precision of the National Institute for Occupational Safety and Health (NIOSH) 5040 sampling and analytical method for diesel exhaust that has recently been adopted for compliance monitoring by the Mine Safety and Health Administration (MSHA). Approximately 1000 air samples using cyclones were taken on workers and in areas throughout the mines. Results indicated that worker exposures were consistently above the MSHA final limit of 160 micrograms/m3 (time-weighted average; TWA) for total carbon as determined by the NIOSH 5040 method and greater than the proposed American Conference of Governmental Industrial Hygienists TLV limit of 20 micrograms/m3 (TWA) for elemental carbon. A number of difficulties were documented when sampling for diesel exhaust using organic carbon: high and variable blank values from filters, a high variability (+/- 20%) from duplicate punches from the same sampling filter, a consistent positive interference (+26%) when open-faced monitors were sampled side-by-side with cyclones, poor correlation (r 2 = 0.38) to elemental carbon levels, and an interference from limestone that could not be adequately corrected by acid-washing of filters. The sampling and analytical precision (relative standard deviation) was approximately 11% for elemental carbon, 17% for organic carbon, and 11% for total carbon. An hypothesis is presented and supported with data that gaseous organic carbon constituents of diesel exhaust adsorb onto not only the submicron elemental carbon particles found in diesel exhaust, but also mining ore dusts. Such mining dusts are mostly nonrespirable and should not be considered equivalent to submicron diesel particulates in their potential for adverse pulmonary effects. It is recommended that size-selective sampling be employed, rather than open-faced monitoring, when using the NIOSH 5040 method.

Phosgene exposure: mechanisms of injury and treatment strategies.

Phosgene (carbonyl chloride, CAS 75-44-5) is a highly reactive gas of historical interest and current industrial importance. Phosgene has also proved to be a useful model for the study of those biochemical mechanisms that lead to permeability-type pulmonary edema (adult respiratory distress syndrome). In turn, the study of phosgene-induced adult respiratory distress syndrome has provided insights leading to revised treatment strategies for exposure victims. We summarized recent findings on the mechanisms of phosgene-induced pulmonary edema and their implications for victim management. In light of that research, we also provide a comprehensive approach to the management and treatment of phosgene exposure victims.

Erratum: Does aluminum exposure of pregnant animals lead to accumulation in mothers of their offspring?

Borak J, Wise JP. 1998. Does aluminum exposure of pregnant animals lead to accumulation in mothers of their offspring? Teratology 57:127-139 In response to the article referenced above, Drs. M. Golub and J. Domingo wrote a Letter to the Editor (Teratology 1998;58:225). Included in that letter was the following statement: "We also urge Drs. Borak and Wise to fulfill their ethical obligation to acknowledge sources of support when submitting manuscripts for publication." This comment would not have been necessary if the article by Borak and Wise had included an acknowledgment of their outside support in their article. The authors had disclosed this outside support in the cover letter to the editor when the manuscript was supplied initially and later after revisions. They did not include an Acknowledgment section in the manuscript. The editorial office should have suggested that they do that. We apologize for any confusion this caused.

Copper exposure and metal fume fever: lack of evidence for a causal relationship.

A systematic search was made of the world literature concerned with possible adverse health effects of inhalation exposure to copper fume and dust. Seven reports published over the past 88 years were identified that contain original human data and purport to document that exposure to copper dust or fume caused metal fume fever (MFF) or an MFF-like syndrome. Insufficient evidence was found to conclude that exposures to copper dust and copper fume cause MFF. Limitations included absence of exposure measurements, atypical symptoms and complaints, and lack of consistency among types of work associated with symptoms. Given the extensive use of copper in many industries and operations, it is evident that if copper-induced MFF does occur, it is a rare event.

[Treatment outcome in tobacco dependence after nicotine replacement therapy and group therapy]. / Wyniki leczenia uzaleznienia od tytoniu za pomoca nikotynowej terapii zastepczej oraz terapii grupowej.

The deletorious health effects of smoking are generally known. In spite of that, great numbers of people still smoke tobacco in the whole world. It is primarily due to the addictive properties of nicotine. Cigarette smoking is also dependent on various social and psychologic factors making quitting very difficult. Among various treatment modalities for tobacco dependence we aimed to assess the efficacy of nicotine replacement therapy (NRT) vs group therapy. 325 subjects smoking at least 15 cigarettes/day for more than 3 years were studied. They were allocated to group therapy (neurolinguistic programming) or NRT (gum or patch) at their will. Non-smoking was validated at each of follow-up visits, at 1 and 2 weeks 1, 3, 6, 12 months by measuring CO in expired air. All groups were matched in age, smoking history and nicotine dependence. The best quit rate was observed as a result of group therapy (41% at 1 year, p. < 0.001) as compared to nicotine patch (2%) and nicotine gum (9%).

Emotional status does not alter exercise tolerance in patients with chronic obstructive pulmonary disease.

Exercise tolerance in chronic obstructive pulmonary disease (COPD) patients has been shown to be related to airway limitation and dyspnoea, but little is known about the effects of an emotional status on physical performance. We examined 49 COPD patients with a wide spectrum of airway limitation severity and hypoxaemia. Exercise tolerance was evaluated using the Six-minute Walking Distance Test (6MWD), dyspnoea at rest and on exercise was measured using the visual analogue scale, and the emotional status was evaluated using the battery of psychological tests. The average 6MWD (mean+/-SD) was 355+/-112 m. In the majority of patients a fall in arterial blood oxygen saturation (Sa,O2) on exercise of >3% was found. The mean dyspnoea score of 21+/-19 at rest increased to 66+/-19 on exercise. All subjects demonstrated an increased level of anxiety. The majority also demonstrated elevated emotional tension, and half of the study group showed signs of depression. Step-wise multiple regression analysis with results of 6MWD as dependent and other studied variables as independent variables showed that exercise tolerance depended mainly on airway limitation. The forced expiratory volume in one second (FEV1) explained 24% of the variance. The forced vital capacity added a further 10%, and arterial blood carbon dioxide tension contributed 7%. The dyspnoea level on exercise added only 0.9%. All four variables explained 42% of the variance. There was no correlation between 6MWD and any of the variables characterizing the emotional status. We conclude that the emotional status of chronic obstructive pulmonary disease patients is characterized by an increased level of psychological tension, anxiety and depression, but these do not affect exercise tolerance as assessed by the six-minute walking distance test.

Does aluminum exposure of pregnant animals lead to accumulation in mothers or their offspring?

There is concern that environmental and dietary aluminum (Al) might cause developmental toxicity. To better understand this concern, we reviewed published studies which administered Al compounds to pregnant animals and measured accumulation of Al in mother, fetus, or born offspring. A total of 7 studies were identified which administered Al during gestation and evaluated fetal accumulation. Another 7 studies administered Al at least until birth and then evaluated accumulation in mothers and/or pups. These 14 studies included 4 different Al compounds (hydroxide, chloride, lactate, and citrate) administered by 4 different routes (gavage, feed, intraperitoneal injection, and subcutaneous injection) with total doses ranging from 13.5 to 8,400 mg/kg. Fetal Al levels were not increased in 6 of 7 studies and pup Al levels were not increased in 4 of 5 studies in which they were measured. Maternal Al levels were increased in some studies, but there was no consistent pattern of organ-specific accumulation and several positive studies were contradicted by subsequent reports from the same laboratory. Placental levels were increased in 6 of 9 studies and were greater than corresponding fetal levels. The weight of evidence in these studies suggests that environmental and dietary Al exposures are unlikely to pose risks of Al accumulation to pregnant animals or their fetuses.

Effects of CPAP treatment on psychological status in patients with severe obstructive sleep apnoea.

The aim of this study was to evaluate the effects of nocturnal continuous positive airway pressure (CPAP) breathing on the emotional status and cognitive function in 20 patients with severe obstructive sleep apnoea (OSA) (mean +/- SD apnoea/hypopnoea index = 67 +/- 16, mean overnight arterial oxygen saturation = 83 +/- 10%). Psychological tests were performed before, after three, and after twelve months of CPAP treatment. At initial investigation, amongst cognitive functions, the most disturbed were concentration and recent memory. The majority of subjects demonstrated increased mental stress, depression, and anxiety. Anxiety correlated with AHI (r = 0.68). Mental stress correlated with AHI (r = 0.56) and deficiency of Stage 2 NREM sleep (r = -0.55). CPAP treatment resulted in significant improvement in cognitive function; concentration, recent verbal, visual and spatial memory were already seen at three months. No improvement in IQ and in emotional status after three months and one year of treatment was found. It is concluded that in patients with severe OSA CPAP treatment results in a significant early improvement in cognitive function but not in emotional status.

Psychological status of COPD patients before and after one year of long-term oxygen therapy.

Cognitive function, psychological status, and attitudes were investigated in 90 patients with chronic obstructive pulmonary disease before the initiation of long-term oxygen therapy and after one year of treatment. Assessment included clinical interview, Wechsler Intelligence Scale I.Q., Bourdon-Wiersma Test, Benton Verbal Retention Test, Rey's Test of Remembering 15 Words, Beck's Depression Scale, Taylor's Manifest Anxiety Scale, and Tylka's Psychological Evaluation Scale of the Effectiveness of Rehabilitation. The mean I.Q. of the patients studied was slightly above average at 107 points. Tests of cognitive function showed reduced performance. These included tests of repeating numbers, pictorial anecdotes and numerical symbols. Rey's Test of Word Memory was also below average but increased following treatment. In the Bourdon Test, there were 58 correct deletions and 7 omissions initially, improving to 67 and 8, respectively, after treatment. Poor visual and spatial memory did not improve after treatment. Before treatment, patients demonstrated depressed mood, low self-esteem with narrow interests, signs of anxiety, mental stress and depression. After a year of long-term oxygen therapy significant improvements in mood and attitudes were demonstrated. We conclude that long-term oxygen therapy may be capable of producing a significant improvement in emotional status. However, the effects of oxygen treatment are difficult to separate from effects of other aspects of care in producing a sense of increased security and well-being.