Techniques for assessing small airways function: Possible applications in asthma and COPD.

In recent years special interest has been expressed for the contribution of small airways in the pathophysiology, clinical manifestations and treatment of asthma and COPD. Small airways contribute little to the total respiratory resistance so that extensive damage of small airways may occur before the appearance of any symptoms, and this is the reason why they are characterized as the "silent zone" of airways. Furthermore, the peripheral localization of the small airways and their small diameter constitutes difficult their direct assessment. Thus, they are usually studied indirectly, taking advantage of the effects of their obstruction, such as premature closure, air trapping, heterogeneity of ventilation, and lung volume dependence of airflow limitation. Today, several heterogeneous methods for the assessment of small airways are available. These can be either functional (spirometry, plethysmography, resistance measurements, nitrogen washout, alveolar nitric oxide, frequency dependence of compliance, flow-volume curves breathing mixture of helium-oxygen) or imaging (mainly through high resolution computed tomography). The above-mentioned methods are summarized in Table 1. However, no method is currently considered as the "gold standard" and it seems that combinations of tests are needed. Furthermore, it is not clear whether the small airways are affected in all patients with asthma or COPD and their clinical significance remains under investigation. Well-designed future studies with large numbers of patients are expected to reveal which of the methods for assessing the small airways is the most accurate, reliable and reproducible, for which patients, and which can be used for the evaluation of the effects of treatment.

Exhaled nitric oxide as screening tool in subjects with suspected asthma without reversibility.

BACKGROUND: As fractional exhaled nitric oxide (FeNO) has been evaluated only in certain settings for asthma diagnosis, we investigated whether FeNO values could predict positive methacholine challenge testing (expressed as PD20) in subjects with suspected asthma but without spirometric reversibility. METHODS: Subjects with asthma-like symptoms and negative bronchodilation test were initially evaluated to undergo FeNO measurement and methacholine bronchial challenge. Diagnostic performance of FeNO to predict PD20 to methacholine <800 µg was examined by constructing receiver-operating characteristic curves. RESULTS: A total of 112 subjects met the inclusion criteria. In all subjects, FeNO >32 ppb was associated with a sensitivity of 0.47 and a specificity of 0.85 for the identification of the PD20 <800 µg (AUC = 0.691, 95% CI = 0.6-0.775, p = 0.00002). In smokers, FeNO >11 ppb was associated with a sensitivity of 0.85 and a specificity of 0.5 for the identification of PD20 <800 µg (AUC = 0.625, 95% CI = 0.45-0.772, p = 0.18), while in atopics a FeNO level >26 ppb was associated with a sensitivity of 0.55 and a specificity of 0.85 (AUC = 0.677, 95% CI = 0.53-0.8, p = 0.02). CONCLUSIONS: In subjects with symptoms compatible with asthma but without spirometric reversibility, specific cutoff levels for FeNO levels significantly predict the positive methacholine challenge, with significant confounding factors being atopy and current smoking.

Development and preliminary validation of a patient-reported outcome measure for swallowing after total laryngectomy (SOAL questionnaire).

OBJECTIVES: To develop and validate a laryngectomee-specific questionnaire to investigate swallowing function. This paper describes the generation of questionnaire items, pretesting with laryngectomees and a preliminary validation. DESIGN: This study employed 2 phases: questionnaire development and questionnaire validation. Items were developed from patient (n = 10) and clinician (n = 6) focus groups. Content checking, acceptability and face validity were determined through pretesting with 10 laryngectomees and via consensus feedback from 35 speech and language therapists. During preliminary validation, the 17-item final questionnaire was administered to 3 different groups. Discrimination amongst groups was established by comparing questionnaire responses of a laryngectomee group (n = 19) with known dysphagic (n = 19) and non-dysphagic groups (n = 20). Questionnaire responses from the reference dysphagic group were compared with an instrumental assessment of swallowing, the modified barium swallow (MBS). SETTING: Large urban teaching hospital. PARTICIPANTS: Speech and language therapists, laryngectomees, non-dysphagic volunteers, post-radiotherapy dysphagic patients. MAIN OUTCOME MEASURE: Preliminary validation of SOAL questionnaire. RESULTS: Normal, laryngectomee and dysphagic groups had significantly different SOAL scores, as did laryngectomees with different degrees of swallowing impairment (Kruskall Wallis, P << 0.001). The subjective SOAL score had a strong positive correlation with the reference measure of ratings on the MBS (r = 0.5; P = 0.03). CONCLUSIONS: The swallowing outcome after laryngectomy (SOAL) questionnaire is a simple, self-administered tool to assess swallowing function post-total laryngectomy. Further specific testing with a laryngectomy cohort is necessary for full validation. Its potential value lies in screening for dysphagia in clinics or during long-term follow-up of laryngectomees.

Bronchoalveolar lavage fluid alteration in antioxidant and inflammatory status in lung cancer patients.

BACKGROUND: Increased oxidative and inflammatory markers have been reported in lung cancer patients, but relatively few studies have investigated the presence of antioxidants both in the local lung environment and in the systemic circulation. Furthermore, it is hypothesized that the immune system activation in vivo is regulated by the redox environment. OBJECTIVES: To investigate local and systemically circulating antioxidant and inflammatory mediators in lung cancer patients and potential correlations between them. METHODS: Forty two male patients (mean age 65±8years) with primary lung cancer were studied. Sixteen age and smoking history matched male subjects without any evidence of malignancy served as controls. Total antioxidant status (TAS) and glutathione (GSH), as well as interleukin-1a (IL-1a), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were measured in bronchoalveolar lavage fluid (BALF) and serum samples. RESULTS: A statistically significant increase of TAS and GSH in BALF was observed in lung cancer patients compared to healthy subjects (0.27±0.24 vs. 0.12±0.02mmol/L, p=0.02 and 7.56±4.29 vs. 4.62±2.23µmol/L, p=0.01 respectively). Statistically significant correlations in cancer patients were observed in BALF between TAS and a. IL-1α (r=0.87, p<0.001), b. IL-6 (r=0.52, p=0.001) and c. TNF-α (r=0.67, p<0.001). CONCLUSIONS: Alteration in antioxidant and inflammatory mediator status was found in lung cancer patients both in serum and in BALF compared to healthy subjects matched for smoking history. Moreover, a positive correlation was observed between antioxidants and pro-inflammatory cytokines, but only locally and not systematically.

The (TAAAA)n polymorphism of the SHBG gene in men with the metabolic syndrome.

OBJECTIVE: Low serum Sex Hormone-Binding Globulin (SHBG) has been proposed as an indicator of the Metabolic Syndrome (MS) and cardiovascular disease in men. On the other hand, the (TAAAA)n repeat polymorphism in the SHBG gene has been shown to affect SHBG levels. The possible role of this polymorphism in the MS was examined in the present study. DESIGN: The study population consisted of 83 men with MS aged 54.9±14.8 years and 166 healthy men of the same age. The diagnosis of MS was based on the criteria proposed by the National Cholesterol Education Program - Third Adult Treatment Panel (NCEP-ATP III). The waist circumference was recorded and blood samples were obtained after overnight fasting for biochemical and hormonal tests. The SHBG(TAAAA)N polymorphism was genotyped in peripheral blood leucocytes. RESULTS: Genotype analysis for the (TAAAA)n polymorphism of the SHBG gene in the patients and controls identified 6 alleles having 6-11 TAAAA repeats. Patients with MS had more frequently short-allele genotypes (with 6/6, 6/7, 6/8, 7/7, 7/8 or 8/8 tandem repeats) compared to controls (53% vs. 39.8%, p=0.047). In the entire study population, men homozygous for the 6 TAAAA repeat allele had lower SHBG levels (p=0.01) and higher waist circumference (p=0.006) than men heterozygous or non-carriers of this allele. CONCLUSION: Short SHBG(TAAAA)N allele genotypes may play a role in the development of the MS. The mechanism of this contribution remains unclear.

Increased androgen bioavailability is associated with non-alcoholic fatty liver disease in women with polycystic ovary syndrome.

BACKGROUND: Increased prevalence of abnormal aminotransferase levels and/or ultrasonographic evidence of hepatic steatosis (HS) have been found in women with polycystic ovary syndrome (PCOS). However, factors associated with non-alcoholic fatty liver disease (NAFLD) in PCOS are still under investigation. The aim of this case-control study was to investigate the presence of NAFLD and to assess factors associated with this condition in PCOS patients. METHODS: A prospective study of 57 premenopausal PCOS patients and 60 age- and weight-matched control women, with a history of no or minimal alcohol consumption was conducted. Anthropometric variables, biochemical and hormonal parameters were determined and NAFLD was evaluated by abdominal ultrasonography and biochemical testing, after excluding causes of secondary liver disease. Insulin resistance was assessed by homeostasis model assessment of insulin resistance (HOMA-IR) and free androgen index (FAI) was calculated. RESULTS: PCOS patients had an increased prevalence of HS [21/57 patients (36.8%) versus 12/60 controls (20.0%), P < 0.05] and abnormal (> or =40 IU/l) serum aminotransferase levels [13/57 patients (22.8%) versus 2/60 controls (3.3%), P < 0.01] than controls. All patients and controls with metabolic syndrome had HS. Factors associated with HS were PCOS diagnosis, older age, increased BMI, waist circumference (WC), HOMA-IR and FAI values and decreased high-density lipid cholesterol and sex hormone binding globulin levels. PCOS patients had an OR of 3.55 (95% CI: 1.02-5.35) for HS versus controls, after adjustment for age, BMI and WC. CONCLUSIONS: NAFLD is common in PCOS patients and increased androgen bioavailability may be implicated, in combination with metabolic abnormalities. Liver evaluation is proposed in PCOS patients, especially in those with metabolic syndrome.

Alterations of erythrocyte superoxide dismutase activity in patients suffering from asthma attacks.

BACKGROUND: Oxidant-antioxidant imbalance may play an important role in the development and progression of bronchial asthma. However, the role of blood antioxidants especially in asthma exacerbation has not been fully discussed. OBJECTIVE: This study examines a part of the intracellular antioxidant defense mechanism in asthmatic patients admitted to hospital due to severe exacerbation of their disease. METHODS: Peripheral blood Erythrocyte Superoxide Dismutase (SOD) activity was measured in 38 patients (33 men - 5 women, with a mean age of 56 +/- 2.8 yrs), using a colorimetric method. On the days of admission and discharge the Forced Expiratory Volume in 1 second (FEV1) and the Partial arterial Oxygen pressure (PaO2) were recorded and correlated with SOD activity at the same time. RESULTS: A statistically significant decrease of SOD activity was observed on the day of admission compared to SOD activity on the day of discharge (43.64 +/- 31.78 vs. 96.16 +/- 54.05 units/ml, p < 0.001), suggesting the presence of oxidative stress during an asthma attack. A statistically significant correlation was observed between FEV1 on admission and SOD activity at the same time (r = 0.57, p < 0.001). Furthermore, SOD activity on admission was correlated with PaO2 on discharge (r = 0.55, p < 0.001), as well as SOD on discharge with PaO2 on discharge (r = 0.53, p = 0.001). CONCLUSIONS: Decreased systemic erythrocyte SOD activity was observed during asthma attacks. This activity was correlated with severity criteria such as FEV1 and PaO2. Therefore, it seems that measurement of SOD activity could be a useful tool in the evaluation of an asthma attack. The supplementary administration of antioxidants in the future needs further clarification.

Glaucoma phenotype in a large Swiss pedigree with the myocilin Gly367Arg mutation.

AIMS: To characterize genotype, phenotype, and age-related penetrance in a Swiss pedigree with juvenile open-angle glaucoma (JOAG). METHODS: In a large Swiss family with history of glaucoma and 82 living members of four generations, we conducted molecular analysis and a detailed phenotype characterization in 52 family members. Mutation analysis was carried out using single-strand conformation polymorphism and DNA sequence analyses of the suspected candidate gene, myocilin (MYOC). RESULTS: We detected a Gly367Arg mutation in the MYOC gene of 13 family members. Nine of them (69.2%) had glaucoma: mean IOP 35.3 mm Hg, range 24-50 mm Hg; mean age at diagnosis 34.9 years, range 28-51 years. Two mutation carriers were glaucoma suspects, one (age 15) was unaffected, and one (age 16) not available for clinical examinations. Age-related glaucoma penetrance was 50% at 30 and 78% at 40. Untreated IOP resulted in rapid disease progression, whereas good IOP control, usually only by means of filtration surgery, could stabilize the disease. None of the wild-type members had glaucoma. CONCLUSIONS: This Swiss family is the largest reported Gly367Arg pedigree to date. The exact genotype and phenotype characterization allowed a reliable risk and prognosis assessment and targeted eye-care planning for the family. The study demonstrates the importance of genetic investigations in glaucoma families, carrying the potential of long-term socio-economic benefits.

Comparison of rebound tonometry with Goldmann applanation tonometry and correlation with central corneal thickness.

BACKGROUND/AIMS: Rebound tonometry (RT) is performed without anaesthesia with a hand held device. The primary aim was to compare RT with Goldmann applanation tonometry (GAT) and to correlate with central corneal thickness (CCT). The secondary aim was to prove tolerability and practicability of RT under "study conditions" and "routine practice conditions." METHODS: In group 1 (52 eyes/28 patients), all measurements were taken by the same physician, in the same room and order: non-contact optical pachymetry, RT, slit lamp inspection, GAT. Patients were questioned about discomfort or pain. In group 2 (49 eyes/27 patients), tonometry was performed by three other physicians during routine examinations. RESULTS: RT was well tolerated and safe. Intraocular pressure (IOP) ranged between 6 mm Hg and 48 mm Hg. No different trends were found between the groups. RT tended to give slightly higher readings: n = 101, mean difference 1.0 (SD 2.17) mm Hg; 84.1% of RT readings within plus or minus 3 mm Hg of GAT; 95% confidence interval in the Bland-Altman analysis -3.2 mm Hg to +5.2 mm Hg. Both RT and GAT showed a weak positive correlation with CCT (r2 0.028 and 0.025, respectively). CONCLUSIONS: RT can be considered a reliable alternative for clinical screening and in cases where positioning of the head at the slit lamp is impossible or topical preparations are to be avoided.

Total antioxidant status and severity of community-acquired pneumonia: are they correlated?

BACKGROUND: Oxidant/antioxidant imbalance has been reported in various respiratory diseases including pneumonia. However, the role of blood antioxidants has not been fully discussed. OBJECTIVES: The aim of this exploratory study was to assess serum total antioxidant status (TAS) in patients with community-acquired pneumonia (CAP) and the probable correlation with the severity of the disease. METHODS: Thirty patients (22 men, 8 women; mean age of 48 +/- 21 years) and 10 healthy nonsmokers (mean age 44 +/- 16 years) were studied. Clinical, laboratory and radiological findings were recorded on the day of admission and on the 7th day. A severity score was calculated using the Fine scale. Serum TAS was measured at the same time points using a colorimetric method. RESULTS: On admission, TAS (TAS1) was significantly lower than on the 7th day (TAS2) (0.84 +/- 0.13 mmo/l vs. 1.00 +/- 0.17 mmo/l; p = 0.0001) and compared with the healthy subjects (0.84 +/- 0.13 vs. 1.19 +/- 0.09 mmol/l; p < 0.001). TAS change (TAS2 - TAS1) was statistically significantly more marked in smokers (0.17 vs. 0.28, p = 0.001), in patients with factors predisposing to CAP (0.12 vs. 0.37; p = 0.000) and in patients with gram-negative pneumonia (0.16 vs. 0.35; p = 0.000). On the other hand, change in TAS was statistically significantly less marked in patients with lobar pneumonia (0.27 vs. 0.17; p = 0.001). Additionally, TAS change was positively correlated to white blood count on admission (r = 0.39; p = 0.029). CONCLUSIONS: It is concluded that serum TAS is decreased in patients with CAP, suggesting the presence of oxidative stress, and that change in TAS seems to be influenced by disease severity. TAS measurement may be useful in estimating the severity of CAP and is a probable indication for the administration of antioxidants in the management of the disease.

Serum total antioxidant status in severe exacerbation of asthma: correlation with the severity of the disease.

Oxidative processes, mediated by oxygen free radicals are recognized to contribute significantly to the inflammatory pathology of bronchial asthma. An imbalance between oxidants and antioxidants has also been proposed in this disease. This study examines the serum total antioxidant status (TAS) in asthmatic patients with severe exacerbation of their disease and the probable correlation with clinical or laboratory findings. The TAS was measured in 20 patients (10 men and 10 women, with a mean age of 41.95 +/- 20.75 years), using a colorimetric method. On the days of admission and discharge, the forced expiratory volume in 1 sec (FEV1), the partial arterial oxygen pressure (PaO2), and severity criteria were recorded and correlated with TAS at the same time. The TAS was also measured in 10 healthy subjects (8 men and 2 women, mean age of 39 +/- 9 years). A statistically significant decrease of TAS was observed on admission day compared to that on discharge day (0.98 +/- 0.08 vs. 1.12 +/- 0.17 mmol/L, p < 0.001, respectively, paired t-test) suggesting the presence of oxidative stress during an asthma attack. The TAS on admission was also statistically significantly decreased compared to that of normal subjects (0.98 +/- 0.08 vs. 1.19 +/- 0.09 mmo/L, p < 0.001, respectively, paired t-test). A statistically significant correlation was observed between FEV1 change and TAS change, from admission to discharge day (r = 0.58, p = 0.007, Pearson correlation). Finally, a statistically significant correlation was found between FEV1 change and TAS on discharge day (r = 0.65, p = 0.002). Decreased TAS was found during an asthma attack, probably as a consequence of increased oxidative stress. The TAS change was correlated with severity criteria, such as FEV1. Therefore, it seems that measurement of TAS could be a simple and useful tool in the evaluation of an asthma attack. The supplementary administration of antioxidants in future needs further clarification.

Serum concentrations of lignocaine before, during and after fiberoptic bronchoscopy.

BACKGROUND: Lignocaine is commonly used for local anesthesia during fiberoptic bronchoscopy (FOB). Several studies have reported the peak serum concentration of lignocaine in relation to time, but most of them did not specify the administered dose of lignocaine gel and its possible correlation with peak serum concentration. OBJECTIVE: The aim of our study was to record the plasma concentrations of lignocaine before, during and after FOB and to evaluate whether the doses for nasal and tracheobronchial anesthesia have any correlation with the peak serum concentrations of the drug. METHODS: Twelve patients with no comorbid conditions undergoing FOB were studied. Lignocaine was administered as a 2% solution using a larynx syringe, 2% gel (mean dose 182.5 +/- 15 mg) and finally 2% solution through the bronchoscope (mean dose 339 +/- 12 mg). Total dose was 622 +/- 20 mg. Venous blood samples were taken before the beginning of local anesthesia and then at 5, 10, 20, 60, 90 and 120 min thereafter. RESULTS: Our results showed that peak plasma concentrations of lignocaine were observed in 8 patients 20 min after the beginning of local anesthesia, in 3 patients 30 min afterwards and in 1 patient 60 min afterwards (2.15 +/- 0.4 microg/ml, 1.9 +/- 0.3 microg/ml, 1. 81 microg/ml, respectively). None of our patients exceeded the critical level of toxicity (5 microg/ml). Both the total and tracheobronchial doses of lignocaine were significantly correlated with peak serum concentration (r = 0.63, p = 0.05 and r = 0.64, p = 0.02, respectively). No correlation was found between the dose for nasal anesthesia and peak serum concentration. No adverse reactions were observed. CONCLUSIONS: In conclusion our data show that although the amount of lignocaine used in this study exceeded the recommended highest dose (400 mg) in all patients, no toxic levels were observed. Peak plasma concentrations were found within 20-30 min from the beginning of local anesthesia. The dose for the anesthesia of nasal mucosa represented a significant percentage of the total dose, but did not correlate with the peak serum concentration of the drug.

Unilateral hypertranslucency of the left hemithorax due to aneurysm of the thoracic aorta.

A 19 year old man presented with a six months history of dyspnoea on exertion. Chest radiographs, isotopic lung scans, and computed tomographic scans of the chest showed unilateral translucency of the left lung, absence of ventilation and perfusion in the same lung, and a 3.5 cm aneurysm of the descending thoracic aorta which compressed the left mainstem bronchus.