Oropharyngeal flora as a source of bacteria colonizing the lower airways in patients on artificial ventilation

During 1 year 27 patients admitted to the respiratory intensive care unit were monitored bacteriologically for a minimum of 10 days (mean: 26.7 days). Oropharyngeal swabs and tracheal aspirates were qualitatively and semi-quantitatively cultured twice weekly. A correlation between oropharyngeal and tracheal flora was found: once a bacterial species colonized the oropharyngeal cavity in high numbers, the identical microorganism was frequently isolated (>50%) from the lower respiratory tract. Six of the 27 patients acquired an infection of the lower airways in the respiratory intensive care unit. The bacteria involved belonged to the patients oropharyngeal flora: S. aureus, Enterobacteriaceae and Pseudomonadaceae. As a result of this study showing the oropharynx to be the source of lower airway colonization/infection, a policy for infection prevention has been outlined. This policy is based on the concept of source elimination by means of oropharyngeal decontamination.     

Pharmacokinetics of a microcrystalline theophylline preparation in patients with chronic obstructive airways disease

Summary Plasma theophylline concentrations have been measured in 9 patients with chronic obstructive airways disease following the oral administration of a microcrystalline theophylline preparation. Some measurements of FEV₁ were also made. Four patients were given 375 mg as a single dose and then subsequently 375 mg stat and 125 mg 4 times daily for 3 days, (Group I). A further 5 patients took 250 mg as a single dose and then 250 mg 4 times daily for 3 days, (Group II). In both groups, following the single dose and again after the last dose of chronic administration, blood samples were obtained at frequent intervals up to 24 h for plasma drug estimation. During the 3-day course, blood samples were drawn before and 2 h after each morning dose. In Group I patients, substantial plasma theophylline concentrations were seen only after the loading dose. Thereafter, the mean concentrations before or 2 h after the morning doese were always less than 4.0 µg/ml. Trough concentrations were usually below 2.0 µg/ml. In contrast patients in Group II achieved substantially higher plasma theophylline concentrations, with mean peak concentrations always 10 µg/ml or greater, and trough concentrations greater than 5 µg/ml on at least one occasion in every subject. The elimination half-lives after chronic administration in both groups were not significantly different from those obtained after single doses. Mean drug accumulation, measured as AUC_ss/AUC₁, was 0.87±0.07 in Group I and 0.72±0.14 in Group II, indicating that accumulation had not occurred with either regimen. The mean increase in FEV₁ 2 h after the administration of a single dose was 19.2% after 375 mg and 16.7% after 250 mg. These results indicate that the recommended dosage regimen for microcrystalline theophylline preparation (375 mg stat and 125 mg 4 times daily) produces inadequate plasma theophylline concentrations: 250 mg 4 times daily would appear to be likely to result in satisfactory theophylline levels in more patients.     

Humidified high flow nasal cannulae: current practice in Australasian nurseries, a survey

Aim: Humidified High Flow Nasal Cannula (HHFNC) has been increasingly adopted as a new means of respiratory support throughout the world. However, evidence to support its safety and efficacy is limited. The aim of the present survey was to determine current practices regarding the usage of HHFNC by neonatologists in Australia and New Zealand. Methods: Surveys were sent to all 167 neonatologists identified by the list of centres in the Australia and New Zealand Neonatal Network. Results: A total of 157 surveys were sent to valid email addresses: 111 (71%) responded of which 105 (67%) had completed the questionnaire. HHFNC is used in 17 (63%) of neonatal intensive care units in Australia and New Zealand. It is most commonly used to reduce nasal trauma (91%) and provide continuous positive airways pressure (62%). The main perceived benefits of HHFNC were the easier application and care of the infant (86%), and improved tolerance by the baby (84%). Rain out leading to fluid instillation into the upper airway (59%) was the most common problem. Conclusion: This survey has provided a snapshot of the practice of HHFNC usage in Australia and New Zealand in 2010 and has revealed that HHFNC use is widespread and that clinical practices are diverse. The majority of neonatologists acknowledge that there is limited evidence to support its efficacy and safety, and would be happy to participate in clinical trials to address how best to deliver HHFNC.     

Long-term outcomes of early-onset wheeze and asthma

Evidence from longitudinal cohort studies demonstrates that wheezing that begins in early life and continues into the school years generally persists into adulthood. This persistent wheezing is associated with lung function deficits and airways hyperresponsiveness that appear to be established in the first few years of life. Allergic sensitization early in life, early-life infection with rhinovirus, or colonization with any of a number of bacteria have been associated with increased risk of persistent wheeze. Early life, whether in utero or in the first few years of life, presents a window of vulnerability during which airway injury results in persistent airways dysfunction. Available data further suggest that a second such window of vulnerability might be present in the preadolescent and adolescent years. Lung function growth patterns established by age 6 years generally continue into early adulthood to middle adulthood, typically leaving groups of subjects with wheezing that persists into or relapses during adulthood with a mean FEV(1) of about 10% of predicted value less than their peers who do not wheeze. Subgroups of patients with persistent asthma, however, can have progressive decreases in lung function and enter adulthood with even lower lung function. The concern exists that these deficits in lung function apparent in early adulthood might put subjects at risk for the later development of chronic obstructive pulmonary disease.     

Targeting small airways, a step further in asthma management

Introduction: During the last decade, small airway (SA) involvement in asthma and Chronic Obstructive Pulmonary Disease (COPD) have reached increasing attention. Originally referred to as the ‘silent zone’, SA may not be that silent after all. Important clinical correlates are asthma exacerbations and airways remodelling, exercise asthma and nocturnal asthma. Thus, to control pathology in the SA has become a desirable goal in asthma management. Objectives: The scope of this review is to give a brief overview of the current status on SA in asthma, how to monitor and to diagnose SA inflammation and finally highlight some important treatment strategies. Results/Conclusion: New tools have been developed to monitor SA function; these implies the use of imaging techniques and respiratory physiology, targeting SA function. Fractional exhaled nitric oxide and the combined use of hyperresponsiveness testing with impulsoscillometry is another option. The introduction of ultrafine aerosols has provided new tools for to treat SA inflammation. The challenge for the future will be to define the optimal particle size and device for maximal deposition in entire lung, including the small airways. Moreover, we also need strategies for increasing the therapeutic ratio, i.e. increasing lung deposition without increasing systemic side effects. Another challenge is to design and to perform clinical trials, targeting effects in SA, proving the clinical importance of SA treatment in a large number of patients. The latter also imply education of our medical authorities, communicating that asthma is more than a beta‐2 agonist responsive central airway disorder of the lungs. Please cite this paper as: Bjermer L. Targeting small airways, a step further in asthma management. Clin Respir J 2011; 5: 131–135.     

Validity of Measurement of Two Specific Biomarkers for the Assessment of Small Airways Inflammation in Asthma

Background: Small airways inflammation in asthma has been supposed to contribute to instability of the disease and therapy resistance. This study was designed to determine the validity of measurement of N^ε-(carboxymethyl)lysine (CML) levels in induced sputum and alveolar concentrations of nitric oxide (NO) for the assessment of small airways inflammation in asthma. Methods: The authors measured CML levels in induced sputum and the bronchial flux (Jno) and alveolar concentration (C_alv) of NO in 37 asthmatic patients and 15 normal controls. After initial analysis, all asthmatics were randomly assigned to receive inhaled fluticasone propionate (FP; 400 μg/day, n = 21) or hydrofluoroalkane–beclomethasone dipropionate (HFA-BDP; 400 μg/day, n = 16) for 12 weeks. And then the determination of exhaled NO level and sputum induction was performed after the treatment period. Results. CML levels in induced sputum were significantly higher in asthmatics than in normal controls (median [interquartile range], asthmatics: 53.0 [44.8–64.3] μg/ml, normal controls: 22.0 [14.8–28.3] μg/ml; p < .01). Similarly, Jno and C_alv were also higher in asthmatics. Moreover, CML level was closely correlated with C_alv but not with Jno in asthmatics (r = .47, p = .005). Jno was significantly correlated with forced expiratory volume in one second/forced vital capacity (FEV₁/FVC), and CML level and C_alv were correlated with forced expiratory flow between 25% and 75% of FVC (FEF_25–75), an index of small airways obstruction. After FP treatment, the decrease in CML level and Calv were very small. In contrast, these levels were markedly decreased after HFA-BDP treatment. Moreover, even after FP or HFA-BDP treatment, CML level was significantly correlated with C_alv. Conclusions: This novel, noninvasive technique of measurement of CML levels in induced sputum and C_alv may prove to be important not only in the evaluation of small airways inflammation but also in helping us move toward a better understanding of the roles of the small airways in the pathogenesis of asthma.     

一夜持续正压呼吸道通气治疗对阻塞性睡眠呼吸暂停低通气综合征患者睡眠结构的影响

目的了解一夜持续正压呼吸道通气(CPAP)治疗对阻塞性睡眠呼吸暂停低通气综合征(OSAS)患者睡眠结构的影响。方法经多导睡眠图(PSG)确诊的OSAS患者113例,经CPAP治疗一夜(≥7 h),同时行PSG监测,观察患者治疗前后睡眠结构以及病情严重程度的参数变化。结果经一夜CPAP治疗后,1、2期睡眠占睡眠总时间的比率显著降低,分别为4.5%、10.1%(P<0.05);3、4期睡眠(深睡眠)占睡眠总时间比率增加6.5%(P<0.05),快速眼动睡眠比率增加8.0%(P<0.05)。呼吸紊乱指数(AHI)下降59.6%(P<0.05);最低血氧饱和度、平均血氧饱和度分别增加18.0%、5.0%(P<0.05)。结论一夜CPAP治疗能显著改善睡眠结构,增加患者的深睡眠,降低AHI,增高血氧饱和度。