Drugs for treating infections caused by non-tubercular mycobacteria: a narrative review from the study group on mycobacteria of the Italian Society of Infectious Diseases and Tropical Medicine.

BACKGROUND: Non-tuberculous mycobacteria (NTM) are generally free-living organism, widely distributed in the environment, with sporadic potential to infect. In recent years, there has been a significant increase in the global incidence of NTM-related disease, spanning across all continents and an increased mortality after the diagnosis has been reported. The decisions on whether to treat or not and which drugs to use are complex and require a multidisciplinary approach as well as patients' involvement in the decision process. METHODS AND RESULTS: This review aims at describing the drugs used for treating NTM-associated diseases emphasizing the efficacy, tolerability, optimization strategies as well as possible drugs that might be used in case of intolerance or resistance. We also reviewed data on newer compounds highlighting the lack of randomised clinical trials for many drugs but also encouraging preliminary data for others. We also focused on non-pharmacological interventions that need to be adopted during care of individuals with NTM-associated diseases CONCLUSIONS: Despite insufficient efficacy and poor tolerability this review emphasizes the improvement in patients' care and the needs for future studies in the field of anti-NTM treatments.

Resistance of bmr energy sorghum hybrids to sugarcane borer and fall armyworm / Resistência de híbridos de sorgo energia bmr à broca-da-cana-de-açúcar e lagarta-do-cartucho

Abstract The lower lignin content in plants species with energy potential results in easier cellulose breakdown, making glucose available for ethanol generation. However, higher lignin levels can increase resistance to insect attack. The objective of this work was to evaluate the susceptibility of a bmr-6 biomass sorghum (a mutant genotype with a lower concentration of lignin) to important pests of energy sorghum, Diatraea saccharalis and Spodoptera frugiperda. Experiments were performed in the laboratory and greenhouse to evaluate the development of these pests on the biomass sorghum bmr hybrids BR007, BR008, and TX635 and their respective conventional near-isogenic genotypes (without the bmr gene). The lignin content was higher in non-bmr hybrids, but the evaluated insect variables varied between treatments, not being consistent in just one hybrid or because it is bmr or not. The lowest survival of S. frugiperda was observed in the BR008 hybrid, both bmr and non-bmr. The S. frugiperda injury scores on plants in the greenhouse were high (>7) in all treatments. For D. saccharalis, there was no difference in larval survival in the laboratory, but in the greenhouse, the BR007 hybrid, both bmr and non-bmr, provided greater survival. Due the need to diversify the energy matrix and the fact that greater susceptibility of the bmr hybrids to either pests was not found in this study, these results hold promise for cultivation of these biomass sorghum hybrids for the production of biofuels.

Resumo O menor teor de lignina em espécies de plantas com potencial energético resulta na maior facilidade de quebra da celulose, disponibilizando glicose para geração de etanol. Porém, maiores teores de lignina representa um fator de resistência ao ataque de insetos. O objetivo deste trabalho foi avaliar como importantes pragas do sorgo energia, Diatraea saccharalis e Spodoptera frugiperda, se comportam quanto à alimentação e desempenho em sorgo bmr-6, um genótipo mutante com menor concentração de lignina. Foram realizados experimentos em laboratório e casa de vegetação, avaliando o desenvolvimento destas pragas nos híbridos de sorgo biomassa bmr 007, 008, TX635 e seus respectivos genótipos isogênicos convencionais (sem o gene bmr). O teor de lignina foi maior nos híbridos não bmr, mas nos parâmetros avaliados nos insetos, houve variação entre os tratamentos, não sendo consistente em apenas um híbrido e nem por ser ou não bmr. A menor sobrevivência de S. frugiperda foi verificada no híbrido BR008 tanto bmr quanto não bmr. As notas de injúria por S. frugiperda no sorgo em casa de vegetação foram altas (>7) em todos os tratamentos. Para D. saccharalis, não houve diferença significativa para a sobrevivência larval em laboratório, mas em casa de vegetação o híbrido BR007 tanto bmr quanto não bmr proporcionaram maior sobrevivência. Diante da necessidade de diversificar a matriz energética e o fato de que não foi comprovada neste estudo maior suscetibilidade dos híbridos bmr a ambas as pragas, estes resultados são promissores para o cultivo desses híbridos de sorgo biomassa para produção de biocombustíveis.

Resistance of bmr energy sorghum hybrids to sugarcane borer and fall armyworm

Abstract The lower lignin content in plants species with energy potential results in easier cellulose breakdown, making glucose available for ethanol generation. However, higher lignin levels can increase resistance to insect attack. The objective of this work was to evaluate the susceptibility of a bmr-6 biomass sorghum (a mutant genotype with a lower concentration of lignin) to important pests of energy sorghum, Diatraea saccharalis and Spodoptera frugiperda. Experiments were performed in the laboratory and greenhouse to evaluate the development of these pests on the biomass sorghum bmr hybrids BR007, BR008, and TX635 and their respective conventional near-isogenic genotypes (without the bmr gene). The lignin content was higher in non-bmr hybrids, but the evaluated insect variables varied between treatments, not being consistent in just one hybrid or because it is bmr or not. The lowest survival of S. frugiperda was observed in the BR008 hybrid, both bmr and non-bmr. The S. frugiperda injury scores on plants in the greenhouse were high (>7) in all treatments. For D. saccharalis, there was no difference in larval survival in the laboratory, but in the greenhouse, the BR007 hybrid, both bmr and non-bmr, provided greater survival. Due the need to diversify the energy matrix and the fact that greater susceptibility of the bmr hybrids to either pests was not found in this study, these results hold promise for cultivation of these biomass sorghum hybrids for the production of biofuels.

Resumo O menor teor de lignina em espécies de plantas com potencial energético resulta na maior facilidade de quebra da celulose, disponibilizando glicose para geração de etanol. Porém, maiores teores de lignina representa um fator de resistência ao ataque de insetos. O objetivo deste trabalho foi avaliar como importantes pragas do sorgo energia, Diatraea saccharalis e Spodoptera frugiperda, se comportam quanto à alimentação e desempenho em sorgo bmr-6, um genótipo mutante com menor concentração de lignina. Foram realizados experimentos em laboratório e casa de vegetação, avaliando o desenvolvimento destas pragas nos híbridos de sorgo biomassa bmr 007, 008, TX635 e seus respectivos genótipos isogênicos convencionais (sem o gene bmr). O teor de lignina foi maior nos híbridos não bmr, mas nos parâmetros avaliados nos insetos, houve variação entre os tratamentos, não sendo consistente em apenas um híbrido e nem por ser ou não bmr. A menor sobrevivência de S. frugiperda foi verificada no híbrido BR008 tanto bmr quanto não bmr. As notas de injúria por S. frugiperda no sorgo em casa de vegetação foram altas (>7) em todos os tratamentos. Para D. saccharalis, não houve diferença significativa para a sobrevivência larval em laboratório, mas em casa de vegetação o híbrido BR007 tanto bmr quanto não bmr proporcionaram maior sobrevivência. Diante da necessidade de diversificar a matriz energética e o fato de que não foi comprovada neste estudo maior suscetibilidade dos híbridos bmr a ambas as pragas, estes resultados são promissores para o cultivo desses híbridos de sorgo biomassa para produção de biocombustíveis.

Resistance of sorghum hybrids to sorghum aphid.

The aphid Melanaphis sorghi (Theobald) (Hemiptera: Aphididae), which infest the sorghum crop, has been an economically important pest which have been causing severe damage to sorghum crops in Brazil since 2019. These species have been observed mainly at the end of vegetative stage and beginning of reproductive stage of plants. Their high reproductive rate on sorghum raises concerns about these pests. Therefore, the present study aimed to estimate the life expectancy and fertility tables of Melanaphis sorghi fed on 15 hybrids of grain sorghum, in order to know the resistance characteristics of these materials and understand how plant resistance can help manage this insect. This study was carried out in a laboratory at 26±2 ºC and 60±10% R.H (relative humidity). Fifty insects were kept in each hybrid, each insect was considered one repetition. According to biological parameters and fertility life table, hybrids BRS373, DKB590 and 50A10 were less suitable for the sugarcane aphid multiplication. Thus, these hybrids could be useful to manage this pest, since the population growth speed is one of the worst problems for the implementation of cropping systems. Genotypes AG1090, MSK327 and XGN1305 favored the development of this pest and, when chosen within a cropping system, other management strategies should be considered.

Resistance of bmr energy sorghum hybrids to sugarcane borer and fall armyworm.

The lower lignin content in plants species with energy potential results in easier cellulose breakdown, making glucose available for ethanol generation. However, higher lignin levels can increase resistance to insect attack. The objective of this work was to evaluate the susceptibility of a bmr-6 biomass sorghum (a mutant genotype with a lower concentration of lignin) to important pests of energy sorghum, Diatraea saccharalis and Spodoptera frugiperda. Experiments were performed in the laboratory and greenhouse to evaluate the development of these pests on the biomass sorghum bmr hybrids BR007, BR008, and TX635 and their respective conventional near-isogenic genotypes (without the bmr gene). The lignin content was higher in non-bmr hybrids, but the evaluated insect variables varied between treatments, not being consistent in just one hybrid or because it is bmr or not. The lowest survival of S. frugiperda was observed in the BR008 hybrid, both bmr and non-bmr. The S. frugiperda injury scores on plants in the greenhouse were high (>7) in all treatments. For D. saccharalis, there was no difference in larval survival in the laboratory, but in the greenhouse, the BR007 hybrid, both bmr and non-bmr, provided greater survival. Due the need to diversify the energy matrix and the fact that greater susceptibility of the bmr hybrids to either pests was not found in this study, these results hold promise for cultivation of these biomass sorghum hybrids for the production of biofuels.

Association among agro-industrial traits and simultaneous selection in sweet sorghum.

Sweet sorghum has emerged as an alternative crop for ethanol yield. The breeding of this crop is performed to obtain cultivars with high ethanol yield, which necessarily requires associating favorable phenotypes for multiple traits. Therefore, the aims of this study were to investigate the association between agro-industrial traits related to ethanol yield and identify the promising genotypes considering multiple traits in sweet sorghum. For this purpose, we evaluated 45 genotypes using a 9 x 5 alpha-lattice experimental design with three replications. The traits measured were flowering time, plant height, tons of stalk per hectare, total soluble solids, tons of brix per hectare, juice extraction, total recoverable sugars, and ethanol yield. Analyses were performed after the recovery of inter-block information. The interrelation of the traits was described by genotype-by-trait biplot. For simultaneous selection, the Modified Mulamba and Mock index was used. For almost all of the agro-industrial traits, except for juice extraction, selective accuracy was above 70%. There were significant differences among genotypes for all the traits. The genotype-by-trait biplot evidenced a positive association between most of the traits related to ethanol yield, except for juice extraction, indicating the possibility of indirect selection to obtain more productive genotypes. Some genotypes proved to be promising based on the selection index, as they accumulated phenotypes favorable for the traits of interest.

Path analysis of agro-industrial traits in sweet sorghum.

Sweet sorghum has considerable potential for ethanol production due to its succulent stalks that contain directly fermentable sugars. Since many traits need to be considered in the selection process to breed superior cultivars for ethanol production, then correlations between the traits might be of use to help the breeder define optimal improvement strategies. The aim of this study was to investigate the association between the principal agro-industrial traits in sweet sorghum, and to evaluate the direct and indirect effects of primary and secondary traits on ethanol production per hectare. In total, 45 sweet sorghum genotypes (lineage/hybrids) were evaluated in an experiment designed in an alpha lattice 5 x 9. The data were analyzed using a mixed model approach. A detailed study of simple correlations was accomplished using path analysis. The experimental precision was high, with an accuracy above 76%. The various genotypes showed genetic variation for all agronomic and industrial traits, except stalk diameter. Some agro-industrial traits showed significant simple correlations with ethanol production, but according to the path analysis, some of these traits did not show a significant direct or indirect effect on ethanol production. The results highlighted the primary and secondary traits with practical relevance to sweet sorghum breeding, since they showed director indirect effects on ethanol production.

Adaptability and stability of genotypes of sweet sorghum by GGEBiplot and Toler methods.

Sweet sorghum has considerable potential for ethanol and energy production. The crop is adaptable and can be grown under a wide range of cultivation conditions in marginal areas; however, studies of phenotypic stability are lacking under tropical conditions. Various methods can be used to assess the stability of the crop. Some of these methods generate the same basic information, whereas others provide additional information on genotype x environment (G x E) interactions and/or a description of the genotypes and environments. In this study, we evaluated the complementarity of two methods, GGEBiplot and Toler, with the aim of achieving more detailed information on G x E interactions and their implications for selection of sweet sorghum genotypes. We used data from 25 sorghum genotypes grown in different environments and evaluated the following traits: flowering (FLOW), green mass yield (GMY), total soluble solids (TSS), and tons of Brix per hectare (TBH). Significant G x E interactions were found for all traits. The most stable genotypes identified with the GGEBiplot method were CMSXS643 for FLOW, CMSXS644 and CMSXS647 for GMY, CMSXS646 and CMSXS637 for TSS, and BRS511 and CMSXSS647 for TBH. Especially for TBH, the genotype BRS511 was classified as doubly desirable by the Toler method; however, unlike the result of the GGEBiplot method, the genotype CMSXS647 was also found to be doubly undesirable. The two analytical methods were complementary and enabled a more reliable identification of adapted and stable genotypes.

Lack of association between IgA deficiency and respiratory atopy in young male adults.

BACKGROUND: The issue of atopy and increased serum IgE in IgA deficiency is still a matter of debate. The aim of this study was to evaluate the prevalence of IgA deficiency and its relationship with respiratory atopy. MATERIALS AND METHODS: A retrospective study on 4700 consecutive young males (age range 18-23), who underwent a health screen for admission to the Italian Airforce Academy between 1993 and 1995 was conducted. Serum IgA was measured by immunoturbidimetry and total and specific IgE by fluorescent enzyme immunoassay (Phadiatop FEIA, Pharmacia Cap System). Airway responsiveness was assessed by methacholine challenge. RESULTS: IgA deficiency was detected in 0.34% (16/4700) subjects and atopy was detected in 8.6% (406/4700). The mean IgA was 243 mg/dl (95% CI 107, 442) in the 406 atopic subjects and 238 mg/dl (95% CI 100, 441) in 1544 controls. Only 6 (37.5%) of the IgA deficient subjects had subnormal IgE levels and 6 were positive in the fluorescent EIA. None of the IgA deficient patients presented with respiratory hyper-reactivity. CONCLUSION: Atopy is not more prevalent in young male adult IgA deficient subjects, who rather display a high frequency of recurrent sinusitis.

Neuropeptide expression in the airways of COPD patients and smokers with normal lung function.

Neurogenic mechanisms seem to play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD), as suggested by a number of in vitro data. However, few studies have investigated the presence of neuropeptides in the airways of patients with COPD, and they have yielded conflicting results. The aim of this study is to compare the expression of the neuropeptide substance P (SP), vasoactive intestinal peptide (VIP), and neuropeptide Y (NPY) in the airways of smokers with and without COPD. Surgical lung samples were obtained from 15 smokers with COPD and 16 smokers with normal lung function, who underwent lobectomy for a solitary lung carcinoma. Airway expression and distribution of SP, VIP, and NPY were identified by immunohistochemistry and analyzed by a computerized image analysis system. Compared to smokers with normal lung function, COPD patients exhibited an increased immunoreactivity for SP and VIP, paralleled by a decreased NPY expression in the epithelium and glands, and a decreased expression of all these three neuropeptides in the smooth muscle layer. Therefore, in the present study we have documented a different expression and distribution of the neuropeptides SP, VIP, and NPY in the airways of smokers with and without COPD. These findings suggest a possible involvement of such neuropeptides in the pathogenesis of some changes occurring in COPD.

T cell activation state in the induced sputum of asthmatics treated with budesonide.

Bronchial hyperresponsiveness and airway infiltration with eosinophils and T lymphocytes are key features of asthma. In particular, CD4+ T cells are currently believed to play a pivotal role as initiators and coordinators of the asthmatic inflammatory response and, therefore, they represent a crucial target of corticosteroid treatment. The aim of the present investigation is thus to evaluate, in patients with mild asthma, the effects of inhaled corticosteroid therapy on the following parameters: (i) functional state of CD4+ T cells; (ii) airway eosinophilia; (iii) bronchial hyperresponsiveness to methacholine. The study was completed by twenty asthmatic, atopic subjects, subdivided into two groups of ten and treated for 12 weeks with either inhaled budesonide (200 microg twice daily) or terbutaline alone (500 microg twice daily), respectively. Expression of CD4+ T cell activation markers was measured in induced sputum at baseline and after 1, 4, 8 and 12 weeks of treatment by flow cytometry, which showed a down-regulation of HLA-DR and CD25 surface proteins in the budesonide group, compared with the control group; these differences resulted as being statistically significant through weeks 4-12. Budesonide also induced a quick, sharp reduction in the percentage of eosinophils detectable in induced sputum, as well as a more gradual progressive improvement in airway hyperresponsiveness to methacholine. Therefore, in addition to assessing various indices of bronchial inflammation, flow cytometry can be reliably applied to induced sputum in order to monitor, even in mildly symptomatic patients, the effects of anti-asthma treatments on T cell activation.

Successful treatment of Cryptococcal meningitis with a combination of liposomal amphotericin B, flucytosine and posaconazole: two case reports.

Cryptococcus neoformans CNS infection frequently affects HIV-infected patients and is often lethal, despite antifungal therapy. The most recent treatment guidelines for Cryptococcal meningitis recommend therapy with lyposomal amphotericin B and possible association with flucitosine. However, clinical response rates in HIV-infected patients are not satisfactory, with a persistent high mortality rate and long term therapy is affected by a high risk of major side effects. Posaconazole, the latest broad-spectrum azole, with both in vitro- and in vivo-documented potent activity against C. neoformans, clearly showed no antagonism with amphotericin B, echinocandins or flucytosine and it has both in vitro and in vivo agonistic activity with flucytosine against C. neoformans. We report two cases of successful salvage therapy based on the addition of posaconazole to a standard treatment based on liposomal amphotericin B and Flucytosine. In addition we used posaconazole also in a maintenance therapeutic regimen with no evidence of recurrences in the follow up of these patients. Our report confirms that posaconazole has clinical activity in the CNS against C. neoformans infection. In addition posaconazole showed no antagonism with any other currently available antifungal agent, and was in fact synergistic to some of them (flucytosine); consequently, it seems to be an ideal candidate for antimicrobial combination salvage therapies. Finally posaconazole represents a good alternative to parenteral therapy and an ideal candidate for long-term maintenance therapy due to its competent toxicity profile and oral bioavailability.

Influenza vaccination coverage in elderly people, Campania (Italy), 1999.

A study on the coverage of influenza vaccination among elderly people was carried out. Fity-six per cent of those interviewed had been vaccinated (weighted coverage 50%), compared with the target of 75%, but higher rates were reported in those older than 74 years and those with chronic diseases.

Effects of non-bronchoconstrictive doses of inhaled propranolol on airway responsiveness to methacholine.

OBJECTIVES: The aim of this study was to evaluate the effects of non-bronchoconstrictive doses of propranolol on airway hyperresponsiveness to methacholine. METHODS: Double increasing concentrations (from 0.03 to 64 micrograms/ml) of inhaled propranolol were administered to a study population which included ten patients with mild asthma, ten rhinitics, and ten healthy control subjects. After the baseline bronchial responses to propranolol and methacholine, expressed as the cumulative provocative dose producing a 20% fall in forced expiratory volume in 1 s (PD20FEV1), were assessed, methacholine challenge was repeated after pretreatment with non-bronchoconstrictive doses of propranolol. RESULTS: The pharmacologically induced beta-blockade did not cause any effect in normal individuals, but it worsened airway responsiveness to methacholine in all asthmatics (geometric mean PD20 FEV1: 257 and 87 micrograms, respectively) and some rhinitics (geometric mean PD20 FEV1: 724 and 446 micrograms, respectively). CONCLUSION: Asthmatic patients were extremely sensitive to beta-blockers, whereas we observed a variable response to propranolol within the group of rhinitic subjects. This variability in the latter group is possibly because these individuals had different degrees of airway inflammation, increased parasympathetic activity, and beta-adrenoceptor dysfunction.

Effect of inhaled heparin on water-induced bronchoconstriction in allergic asthmatics.

OBJECTIVE: The aim of this study was to investigate the effect of inhaled heparin on bronchoconstriction induced by ultrasonically nebulised distilled water (UNDW) in allergic asthmatics. METHODS: Eight atopic asthmatics, hyperresponsive to UNDW, were selected for this randomised, placebo-controlled, crossover double-blind study. On two consecutive days, these subjects underwent a UNDW challenge 45 min after inhaling aerosolised heparin (1000 U/kg) or placebo. RESULTS: Neither heparin nor placebo had a significant effect on base-line forced expiratory volume in 1 s (FEV1), but heparin significantly attenuated UNDW-induced bronchoconstriction, as shown by its efficacy in preventing the decreases in FEV1 produced by all doses of water (in comparison with placebo: P < 0.05 after 2 ml water; P < 0.01 after 4, 8 and 16 ml water). CONCLUSION: Inhaled heparin is able to exert a protective effect against the bronchoconstrictive response to UNDW in allergic asthmatics, and this action is likely due to inhibition of mast cell degranulation.

Inhaled beclomethasone dipropionate (BDP) prevents seasonal changes in atopic asthmatics.

Inhaled corticosteroids are most effective drugs currently available for the treatment of bronchial asthma. They have been shown to reduce airway inflammation and hyperresponsiveness. The aim of this study was to assess the preventive effect of inhaled steroid therapy in seasonal asthma. In a double-blind study, two groups of 10 allergic asthmatics were randomly assigned to receive inhaled beclomethasone dipropionate (BDP), 500 micrograms b.i.d., or a matched placebo, two puffs b.i.d. The patients used inhaled salbutamol as needed. At the beginning of the study, and every month between February and June, the following parameters were assessed: lung function (forced expiratory volume in one second (FEV1); airway responsiveness (provocative dose of methacholine producing a 20% fall in forced expiratory volume in one second (PD20)), serum eosinophil cationic protein (ECP); and blood eosinophil count. All subjects recorded daily asthma symptoms, beta 2-agonist consumption and peak expiratory flow (PEF) values. In the placebo group, all parameters except FEV1 worsened significantly during the pollen season compared with preseasonal values (p < 0.001). BDP produced complete protection, although a slight change from baseline was found for symptom score (p < 0.01), beta 2-agonist consumption (p < 0.01), and eosinophil number (p < 0.05) in May, when the pollen load was highest. These data provide evidence that beclomethasone dipropionate treatment is able to inhibit the seasonal changes occurring during natural exposure in asthmatics. This preventive effect is probably due to the anti-inflammatory action of beclamethasone dipropionate, as documented by its effect on serum markers of airway inflammation.

Serum eosinophil cationic protein (ECP) as a marker of disease activity and treatment efficacy in seasonal asthma.

This study was carried out to determine whether serum eosinophil cationic protein (ECP) represents a sensitive marker for disease activity in atopic asthmatic patients during the pollen season. The study, in double-blind fashion, was performed between February and June 1994. Two groups of 10 seasonal asthmatic patients randomly received two different treatments. The first group was treated with inhaled beclomethasone dipropionate (BDP) 500 micrograms bid; the second received a matched placebo (P). At the beginning and every month, blood samples for determination of ECP and eosinophil count were collected and lung function (FEV1) and methacholine responsiveness (PD20) were performed. Subjects recorded daily symptoms of asthma, salbutamol consumption, and peak expiratory flow (PEF) values. In the P group, all indices, except FEV1, showed significant changes during the pollen season (P < 0.001). In the BDP group, significant changes were detected for symptom score (P < 0.01), salbutamol consumption (P < 0.01), and eosinophil number (P < 0.05). Between the two groups, significant differences for symptom score (P < 0.001), salbutamol consumption (P < 0.001), ECP levels (P < 0.05), eosinophil count (P < 0.02), PD20 methacholine (P < 0.02), and PEF values (P < 0.01) were detected. Changes in serum ECP significantly correlated with changes in other parameters (P < 0.001), except FEV1. Our results provide evidence that serum ECP is a sensitive marker for monitoring of the disease activity in seasonal asthma. Furthermore, it may offer a useful tool for estimating treatment efficacy.

Effect of ipratropium bromide and/or sodium cromoglycate pretreatment on water-induced bronchoconstriction in asthma.

The mechanisms underlying water-induced bronchoconstriction are still not fully understood. Cholinergic reflexes and mast cell mediator release are currently believed to play an important pathogenetic role. In order to evaluate the relative contribution of each of these mechanisms, we studied the effect of ipratropium bromide (80 micrograms), a muscarinic antagonist, and sodium cromoglycate (20 mg), an inhibitor of mast cell mediator release, administered alone and in combination, in the prevention of bronchospasm induced by ultrasonic mist of distilled water (UMDW). Fifteen patients with documented atopic asthma and hyperresponsiveness to distilled water were selected for this randomized, placebo-controlled, double-blind study. Airway responses to pharmachological agents and bronchial challenge were measured by change in specific airways conductance (sGaw). Sodium cromoglycate had no effect on bronchial calibre, whilst ipratropium bromide and the combination of the two drugs produced a significant bronchodilation 30, 60 and 90 min after treatments. The maximal increase in sGaw (mean % +/- SD) was observed at 90 min: 63 +/- 28% and 58 +/- 22% after ipratropium bromide and the combined drugs respectively. UMDW (2, 4, 8, 16 ml water) caused a -36 +/- 19%, -42 +/- 19%, -49 +/- 18%, -56 +/- 15% mean % +/- SD fall in sGaw after placebo. Pretreatment with sodium cromoglycate abolished the bronchoconstriction to 2 ml (fall sGaw -5 +/- 23% NS) and significantly reduced the effect of 4 (-15 +/- 22%), 8 (-21 +/- 20%) and 16 ml (-24 +/- 18%) water.(ABSTRACT TRUNCATED AT 250 WORDS)