Tuberculosis screening in outpatient healthcare workers: lessons from a high-income, low TB burden country.

SETTING: Early diagnosis of latent tuberculous infection (LTBI) should be pursued in healthcare workers (HCWs). While HCWs in hospitals are screened for LTBI, HCWs in outpatient settings are usually not. In 2017, in Italy, a tuberculosis (TB) infected paediatrician working in an outpatient vaccination service infected 15 adults and nine children. The investigation involved 2490 children and 151 adults. Among children, nine were tuberculin skin test-positive, and four developed active TB. Among 123 adult contacts with longer exposure, seven were interferon-gamma release assay (IGRA) positive and none had active TB. Among 28 close contacts, eight had a positive IGRA, and three had pulmonary TB. The total outbreak cost €1 017 903.OBJECTIVE: To compare the outbreak cost with those of potential screening programme strategies.RESULTS: Regular screening of paediatric outpatient HCWs would have cost between €2592 and €11 373. Extending the screening to all outpatient HCWs (caring for adults and children) would have cost between €66 384 and €155 043. Investigating only close contacts would have cost €42 857.CONCLUSION: Each of these screening strategies would have been cost-effective compared with the outbreak investigation occurring in real life with a cut-off of 474 for the maximum number of tested outpatient HCWs needed for the screening strategy to be cost-saving.

Tumour infiltrating lymphocytes and PD-L1 expression as potential predictors of outcome in patients with malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare and aggressive form of tumour. Some mesotheliomas have been proven to be highly immunogenic. Here, we investigated the correlation between tumour infiltrating lymphocytes (TILs) or programmed cell death ligand 1 (PD-L1) expression with overall survival (OS) in patients with MPM. 62 Paraffin-embedded formalin fixed (PEFF) samples were analysed for TILs and PD-L1 expression. Patients were divided in 4 groups according to a cut-off of the percentage of TILs found per sample as measured by immunohistichemistry: "0" or absent (between 0 and 5%), "1" or low (between 6 and 25%), "2" or moderate (between 26 and 50%) and "3" or high (between 51 and 75%). OS was then correlated with different TILs' expression patterns. Moreover, PD-L1 expression was assessed within the tumour as well as in the adjacent stroma on the same samples. Higher expression of peritumoral TILs (Group 2 + 3) versus Group 0 and 1 correlated with improved OS (p-value = 0.02). On the contrary PD-L1 expression seemed to be inversely correlated with clinical outcomes, even in the absence of statistical significance (HR 1.76; p = 0.083 95% IC 0.92-3.36 in areas within the tumour; HR 1.60; p = 0.176 95%; IC 0.80-3.19 in areas within the stroma). No relationship between TILs and PD-L1 expression was identified. Our research supports the use of TILs and PD-L1 expression as potential outcome predictors in patients with MPM. The use of TILs and PD-L1 as biomarkers for checkpoint inhibitors' efficacy warrants future investigation.

Efficacy of pirfenidone for idiopathic pulmonary fibrosis: An Italian real life study.

BACKGROUND: In this retrospective Italian study, which involved all major national interstitial lung diseases centers, we evaluated the effect of pirfenidone on disease progression in patients with IPF. METHODS: We retrospectively studied 128 patients diagnosed with mild, moderate or severe IPF, and the decline in lung function monitored during the one-year treatment with pirfenidone was compared with the decline measured during the one-year pre-treatment period. RESULTS: At baseline (first pirfenidone prescription), the mean percentage forced vital capacity (FVC) was 75% (35-143%) of predicted, and the mean percentage diffuse lung capacity (DLCO) was 47% (17-120%) of predicted. Forty-eight patients (37.5%) had mild disease (GAP index stage I), 64 patients (50%) had moderate IPF (stage II), and 8 patients (6.3%) had severe disease (stage III). In the whole population, pirfenidone attenuated the decline in FVC (p = 0.065), but did not influence the decline in DLCO (p = 0.355) in comparison to the pre-treatment period. Stratification of patients into mild and severe disease groups based on %FVC level at baseline (>75% and ≤75%) revealed that attenuation of decline in FVC (p = 0.002) was more pronounced in second group of patients. Stratification of patients according to GAP index at baseline (stage I vs. II/III) also revealed that attenuation of decline in lung function was more pronounced in patients with more severe disease. CONCLUSIONS: In this national experience, pirfenidone reduced the rate of annual FVC decline (p = 0.065). Since pirfenidone provided significant treatment benefit for patients with moderate-severe disease, our results suggest that the drug may also be effective in patients with more advanced disease.

To use or not to use corticosteroids for pneumonia? A clinician's perspective.

The use of corticosteroids in the management of pneumonia is still a controversial issue. The physicians in daily clinical practice often use corticosteroids in patients with pneumonia for different reasons all over the world. As an example of real life is the frequent use of corticosteroids to treat patients with pneumonia due to H1N1 pandemic influenza in spite of WHO' statements that clearly discouraged this therapy. In fact, the literature up to august 2012 reported a total of 6,650 patients with pneumonia due to H1N1 virus infection (of whom 2,515 were ICU patients): corticosteroids were used with various dose regimen in 2404 patients (37.8%). The attitude of international guidelines on pneumonia in using steroids do not help the clinician to clearly choice when and how to treat pneumonia with steroids. However, stress doses of corticosteroids are suggested by some major guidelines on community-acquired pneumonia in case of severe episodes with sepsis. To date, there are 10 randomised controlled trials assessing the effectiveness of corticosteroids for community-acquired pneumonia globally involving 1090 participants. Most of the trials adopted stress doses of glucorticoids for 4-7 days. The evidence from these trials taken separately is weak due to limitations of the studies themselves, but a Cochrane review and a systematic review found benefit using prolonged low doses of glucocorticoids in severe community-acquired pneumonia. Moreover, such a strategy decreases vasopressor dependency and appears to be safe. Nevertheless, larger trials with more patients and clinically important end-points were claimed to provide robust evidence. Finally, infection surveillance is critical in patients treated with corticosteroids, and to prevent the rebound phenomenon, the drug should be weaned slowly.

Prolonged hospitalisation for immigrants and high risk patients with positive smear pulmonary tuberculosis.

BACKGROUND AND OBJECTIVE: Tuberculosis (TB) occurring in immigrants and resistance to drugs are major problems for TB control in Western countries. Directly observed therapy (DOT) reduces disease transmission, but this approach may have poor results among illegal immigrants. Our aim was to evaluate a prolonged hospitalisation programme to improve early outcome of TB treatment in high risk patients. METHODS: All the consecutive adult patients with sputum smear-positive pulmonary TB admitted to 2 Italian referral TB Centres were evaluated. Hospital-based DOT was provided to high risk patients up-to smear conversion. Demographic, microbiological and clinical conditions, as potential factors associated with confirmed smear conversion at 60 and 90 days of anti-tuberculous therapy were evaluated. RESULTS: 122 patients were studied, 45.9% of them were immigrants (20% illegal) from high-prevalence TB countries. HIV testing was negative in all cases. Twelve patients had M. tuberculosis resistant to > or = 1 first-line anti-tuberculous agents. The rate of defaulting from TB treatment was 73%. Sputum smear became negative in 84.4% cases after 60 days and 933% cases after 90 days. At such time, smear conversion rates were similar among different high risk subgroups such as illegal immigrants (95.9%), legal foreign-born (92.5%) and Italian persons (94.8%). Persistent sputum smear positivity was independently correlated with the extent of pulmonary lesions at 60 (p < 0.0001) and 90 days (p = 0.038) of hospital-based DOT. CONCLUSIONS: These findings suggest that prolonged hospitalisation for illegal immigrants and high risk TB patients, may positively influence the early outcome of TB treatment despite of drug resistance and legal status.

Out-of-hospital helmet CPAP in acute respiratory failure reduces mortality: a study led by nurses.

BACKGROUND AND AIM: Acute respiratory failure (ARF) is a condition that must be treated as quickly as possible. Continuous Positive Airway Pressure (CPAP) is a common method used to treat ARF in hospital. The main objective of our study was to investigate the effect of CPAP prior to admission to the emergency room, on the reduction of endotracheal intubation, in-hospital mortality and on the length of stay in hospital (HLOS). METHODS: A prospective, observational (non-randomised) study with a historical control group. Data from 3 groups of patients with ARF, irrespective of cause, was collected: pre-hospital CPAP (PHCPAP) group, i.e., 35 patients treated with a helmet CPAP in the ambulance, by trained nurses (mean age, years 80.1 +/- 7.9 SD; 14 males); hospital CPAP (HCPAP) group, i.e., 46 patients treated with helmet CPAP in the hospital emergency room (mean age 78.6 +/- 6.9 SD; 27 males), and a historical control group of 125 patients treated with medical therapy only (mean age 76.7 +/- 5.5 SD; 52 males). CPAP was delivered via a helmet interface. RESULTS: Compared with standard medical therapy, helmet CPAP (pre and in-hospital) reduced mortality by 77% (p = 0.005), while pre-hospital helmet CPAP reduced it by 94% (p = 0.011), after adjustment for age, sex, severity of clinical conditions at entry and diagnosis upon admission. HLOS was reduced, compared with standard medical therapy, by 63.5% and by 66% (adjusting for age, sex, severity of clinical conditions at entry and diagnosis at admission) with helmet CPAP (pre and in-hospital) and with helmet CPAP in the ambulance, respectively (p < 0.0001). CONCLUSIONS: Treating patients with ARF of any cause, with CPAP by trained nurses, before hospital admission, is safe, reduces mortality and the length of stay needed in hospital.

Production of transgenic barrel medic (Medicago truncatula Gaernt.) using the ipt-type MAT vector system and impairment of Recombinase-mediated excision events.

Expression of the uidA reporter gene was tested in transformation experiments of barrel medic (Medicago truncatula Gaertn.) with the ipt-type control vectors pIPT5, pIPT10 and pIPT20 and distinct in vitro culture conditions. The highest GUS expression levels were obtained with the pIPT10 construct carrying the ipt gene under the control of the native ipt promoter and using kanamycin as selective agent. The ipt-shooty transformants, characterized by the absence of both rooting ability and apical dominance associated with vitrification, were easily identified by visual selection. Using only the ipt gene as selectable marker, we obtained a stable transformation frequency of 9.8% with pIPT10 construct. The ipt-type MAT vector pEXM2 was then used to monitor the excision events mediated by the yeast Recombinase and the consequent production of ipt marker-free transgenic plants. Transgenic ipt-shooty lines were recovered at a frequency of 7.9% in the absence of kanamycin-based selection. The ipt-shooty phenotype was maintained in all the transgenic lines and no reversion to the normal phenotype occurred. PCR analysis revealed the presence of the 'hit and run' cassette in the genome of all the regenerated ipt-shooty lines while RT-PCR experiments confirmed the expression of the R gene, encoding the yeast Recombinase. A detailed molecular investigation, carried out to verify the integrity of the RS sites, revealed that these regions were intact in most cases. Our results with barrel medic suggest that the MAT system must be carefully evaluated and discussed on a case by case basis.

Efficacy and safety of azithromycin 1 g once daily for 3 days in the treatment of community-acquired pneumonia: an open-label randomised comparison with amoxicillin-clavulanate 875/125 mg twice daily for 7 days.

This randomised, open-label, non-inferiority study was designed to demonstrate that a 3-day course of oral azithromycin 1 g once daily was at least as effective as a standard 7-day course of oral amoxicillin-clavulanate 875/125 mg twice daily in the treatment of outpatients with community-acquired pneumonia (Fine class I and II). In total, 267 patients with clinically and radiologically confirmed community-acquired pneumonia were randomly assigned to receive either the azithromycin (n=136) or the amoxicillin-clavulanate (n=131) regimen. At screening, 60/136 (58.8%) and 61/131 (62.9%) respectively had at least one pathogen identified by sputum culture, PCR, or serology. The primary endpoint was the clinical response in the intent-to-treat population at the end of therapy (day 8 to 12). Clinical success rates were 126/136 (92.6%) for azithromycin and 122/131 (93.1%) for amoxicillin-clavulanate (treatment difference: - 0.48%; 95% confidence interval: - 5.66%; 4.69%). Clinical and radiological success rates at follow-up (day 22-26) were consistent with the end of therapy results, no patient reporting clinical relapse. Bacteriological success rates at the end of therapy were 32/35 (91.4%) for azithromycin and 30/33 (90.9%) for amoxicillin-clavulanate (treatment difference: 0.52%; 95% confidence interval - 10.81%; 11.85%). Both treatment regimens were well tolerated: the overall incidence of adverse events was 34/136 (25.0%) for azithromycin and 22/132 (16.7%) for amoxicillin-clavulanate. In both treatment groups, the most commonly reported events were gastrointestinal symptoms. Azithromycin 1g once daily for 3 days is at least as effective as amoxicillin-clavulanate 875/125 mg twice daily for 7 days in the treatment of adult patients with community-acquired pneumonia.

Out-patient high-dose-rate endobronchial brachytherapy for palliation of lung cancer: an observational study.

BACKGROUND AND AIM: Out-patient high-dose-rate endobronchial brachytherapy (HDREB) is a possible option in the palliation of symptoms in patients with advanced lung cancer, but literature data is limited and the technique is still under development in Italy. Our aim was to evaluate safety and effectiveness of out-patient HDREB for palliation of malignant endobronchial tumours in the context of a multidisciplinary approach. METHODS: Out-patient HDREB sessions were scheduled at weekly intervals (500-1000 cGy per session) with prior Diodi-laser resection in some cases. Response was assessed bronchoscopically, clinically and functionally at the end of treatment and one month after the last HDREB session. Inclusion criteria was: histological evidence of malignant tumour not susceptible to surgical treatment for extension or co-morbidity. RESULTS: 150 outpatient HDREB sessions were carried out on consecutive 35 patients (mean age 69 yrs, M/F 29/6) with symptoms due to central airway obstruction. A shortterm endoscopic response was observed in 15/28 patients. After delivering 2000 cGy dyspnoea decreased significantly. After one month cough decreased and haemoptysis disappeared. Palliation was obtained in all patients except one during. Lung function tests did not significantly improve after HDREB. No fatal complication occurred. A temporary radiation bronchitis was observed in six patients. CONCLUSIONS: This non-comparative, prospective observational study showed a palliative response of HDREB in most of patients with advanced endoluminal lung cancer. The safety of the procedure was good and the rate of non-fatal serious complications was very low.

A chart of failure risk for noninvasive ventilation in patients with COPD exacerbation.

Knowing the likelihood of failure of noninvasive positive pressure ventilation (NPPV) in patients with exacerbation of chronic obstructive pulmonary disease (COPD) could indicate the best choice between NPPV and endotracheal intubation instituted earlier. For this purpose, two risk charts were designed (at admission and after 2 h of NPPV) that included all relevant measurable clinical prognostic indicators derived from a population representing the patients seen routinely in clinical practice. Risk stratification of NPPV failure was assessed in 1,033 consecutive patients admitted to experienced hospital units, including two intensive care units, six respiratory intermediate care units, and five general wards. NPPV was successful in 797 patients. Patients with a Glasgow Coma Score <11, acute physiology and chronic health evaluation (APACHE) II > or =29, respiratory rate > or =30 breaths x min(-1) and pH at admission <7.25 have a predicted risk of failure >70%. A pH <7.25 after 2 h greatly increases the risk (>90%). The risk charts were validated on an independent group of 145 consecutive COPD patients treated with NPPV due to an acute ventilatory failure episode. To identify patients with a probability of failure >50%, the sensitivity and specificity were 33% and 96.7% on admission and 52.9% and 94.1% after 2 h of NPPV, respectively. The prediction chart, based on data from the current study, can function as a simple tool to predict the risk of failure of noninvasive positive pressure ventilation and thus improve clinical management of patients tailoring medical intervention.

Quality of generated diagnosis related groups in Italian Respiratory Intermediate Care Units.

BACKGROUND: To date we lack official data on tipology of Diagnosis Related Groups (DRGs) and their quality in Italian Respiratory Intermediate Care Units (RICUs). AIM: The objective of the study was to collect data on the activity of 26 Italian RICUs and to evaluate the quality of the DRGs generated. METHODS: The primary and secondary diseases, the procedures carried out and their coding using the ICD9 system (valid Italy until 2000) were collected from the discharge forms of patients admitted to RICUs. To obtain the DRG, these codes were automatically recoded in the ICD9-CM classification system by Grouper 10. Afterwards, the same diseases and procedures were directly processed by the ICD9-CM classification system. Finally, in order to evaluate the quality of care, the DRGs generated by the ICD9 classification system were compared to DRGs generated by the ICD9-CM classification system. RESULTS: The average weight of the patients cared for in an Italian RICU was 2.05 using the ICD9 classification system and 2.53 using the ICD9-CM classification system. Some non-complicated DRGs (80-97) or non specific DRGs (101-102) were set to zero; others, like DRG 87 appear due to the ability of the ICD9-CM classification system to recognise and accept the fifth digit of the Respiratory Failure code (518.81). The difference in terms of DRG scores generated by the two codification systems was 360.5 DRG points in favour of ICD9-CM. More than 1 million Euro of reimbursements have been lost, as the average national reimbursement for each DRG score is Euro 2,943.80. CONCLUSION: Severe pulmonary diseases determined the case mix of patients cared for in the Italian RICUs during the observed period. The Italian RICUs offer high quality assistance and are characterised by high mean weight per treated patient. However, the activity has been under-estimated due to the low sensitivity of the ICD9 classification system used in the recognition of the real disease and in the correct generation of relative DRG. The ICD9 classification system penalised the recognition of respiratory failure in particular.

Where to perform noninvasive ventilation?

Noninvasive positive-pressure ventilation (NPPV) has been shown to be a means of reducing the need for endotracheal intubation, which when effective reduces the complication rate and improves outcome. Because paralysis and sedation are not needed and because the patient is not necessarily dependent upon a machine for respiration, ventilation outside the intensive care unit (ICU) is an option. A number of studies have shown that NPPV for acute exacerbations of chronic obstructive pulmonary disease (COPD) can be effective in the non-ICU environment, though usually in patients with less severe exacerbations. However, there have been no direct comparisons of the application of NPPV in different locations. The likelihood of success of the technique is an important factor in deciding there NPPV should be performed. Ready access to invasive ventilation is important when NPPV is not indicated from the outset or fails after an initial trial. In acute exacerbations of COPD, NPPV is less likely to be successful the more severe the exacerbation, as measured by the severity of acidosis. Good tolerance of NPPV, which translates into an improvement in pH and a fall in respiratory rate, predicts a successful outcome and is a useful way of monitoring progress. NPPV has been shown to be cost effective both in the ICU and when performed on general wards. A dedicated intermediate care unit with particular expertise in noninvasive modes of ventilation may provide the best environment, both in terms of outcome, but also cost effectiveness. The ideal location for noninvasive positive-pressure ventilation will vary from country to country and indeed from hospital to hospital, depending upon local factors. However, the most important factor is that staff be adequately trained in the technique and be available throughout the 24-h period.

Clinical relevance of monitoring respiratory mechanics in the ventilator-supported patient: an update (1995-2000).

The introduction of mechanical ventilation in the intensive care unit environment had the merit of putting a potent life-saving tool in the physicians' hands in a number of situations; however, like most sophisticated technologies, it can cause severe side effects and eventually increase mortality if improperly applied. Assessment of respiratory mechanics serves as an aid in understanding the patient-ventilator interactions with the aim to obtain a better performance of the existing ventilator modalities. It has also provided a better understanding of patients' pathophysiology. Thanks to it, new ventilatory strategies and modalities have been developed. Finally, on-line monitoring of respiratory mechanics parameters is going to be more than a future perspective.

Respiratory intensive care units in Italy: a national census and prospective cohort study.

BACKGROUND: In Italy, respiratory intensive care units (RICUs) provide an intermediate level of care between the intensive care unit (ICU) and the general ward for patients with single organ respiratory failure. Because of the lack of official epidemiological data in these units, a two phase study was performed with the aim of describing the work profile in Italian RICUs. METHODS: A national survey of RICUs was conducted from January to March 1997 using a questionnaire which comprised over 30 items regarding location, models of service provision, staff, and equipment. The following criteria were necessary for inclusion of a unit in the survey: (1) a nurse to patient ratio ranging from 1:2.5 to 1:4 per shift; (2) availability of adequate continuous non-invasive monitoring; (3) expertise for non-invasive ventilation (NIV) and for intubation in case of NIV failure; (4) physician availability 24 hours a day. Between November 1997 and January 1998 a 3 month prospective cohort study was performed to survey the patient population admitted to the RICUs. RESULTS: Twenty six RICUs were included in the study: four were located in rehabilitation centres and 22 in general hospitals. In most, the reported nurse to patient ratio ranged from 1:2 to 1:3, with 36% of units reporting a ratio of 1:4 per shift. During the study period 756 consecutive patients of mean (SD) age 68 (12) years were admitted to the 26 RICUs. The highest proportion (47%) were admitted from emergency departments, 19% from other medical wards, 18% were transferred from the ICU, 13% from specialist respiratory wards, and 2% were transferred following surgery. All but 32 had respiratory failure on admission. The reasons for admission to the RICU were: monitoring for expected clinical instability (n=221), mechanical ventilation (n=473), and weaning (n=59); 586 patients needed mechanical ventilation during their stay in the RICU, 425 were treated with non-invasive techniques as a first line of treatment (374 by non-invasive positive pressure, 51 by iron lung), and 161 underwent invasive mechanical ventilation (63 intubated, 98 tracheostomies). All but 48 patients had chronic respiratory disease, mainly chronic obstructive pulmonary disease (COPD; n=451). More than 70% of patients (n=228) had comorbidity, mainly consisting of heart disorders. The median APACHE II score was 18 (range 1--43). The predicted inpatient mortality risk rate according to the APACHE II equation was 22.1% while the actual inpatient mortality rate was 16%. The mean length of stay in the RICU was 12 (11) days. The outcome in most patients (79.2%) admitted to RICUs was favourable. CONCLUSIONS: Italian RICUs are specialised units mainly devoted to the monitoring and treatment of acute on chronic respiratory failure by non-invasive ventilation, but also to weaning from invasive mechanical ventilation. The results of this study provide a useful insight into an increasingly important field of respiratory medicine.

Predictors of failure of noninvasive positive pressure ventilation in patients with acute hypoxemic respiratory failure: a multi-center study.

CONTEXT: In patients with hypoxemic acute respiratory failure (ARF), randomized studies have shown noninvasive positive pressure ventilation (NPPV) to be associated with lower rates of endotracheal intubation. In these patients, predictors of NPPV failure are not well characterized. OBJECTIVE: To investigate variables predictive of NPPV failure in patients with hypoxemic ARF. DESIGN: Prospective, multicenter cohort study. SETTING: Eight Intensive Care Units (ICU) in Europe and USA. PATIENTS: Of 5,847 patients admitted between October 1996 and December 1998, 2,770 met criteria for hypoxemic ARF. Of these, 2,416 were already intubated and 354 were eligible for the study. RESULTS: NPPV failed in 30% (108/354) of patients. The highest intubation rate was observed in patients with ARDS (51%) or community-acquired pneumonia (50%). The lowest intubation rate was observed in patients with cardiogenic pulmonary edema (10%) and pulmonary contusion (18%). Multivariate analysis identified age > 40 years (OR 1.72, 95% CI 0.92-3.23), a simplified acute physiologic score (SAPS II) > or = 35 (OR 1.81, 95% CI 1.07-3.06), the presence of ARDS or community-acquired pneumonia (OR 3.75, 95% CI 2.25-6.24), and a PaO2:FiO2 < or = 146 after 1 h of NPPV (OR 2.51, 95% CI 1.45-4.35) as factors independently associated with failure of NPPV. Patients requiring intubation had a longer duration of ICU stay ( P < 0.001), higher rates of ventilator-associated pneumonia and septic complications ( P < 0.001), and a higher ICU mortality ( P < 0.001). CONCLUSIONS: In hypoxemic ARF, NPPV can be successful in selected populations. When patients have a higher severity score, an older age, ARDS or pneumonia, or fail to improve after 1 h of treatment, the risk of failure is higher.

The appropriate setting of noninvasive pressure support ventilation in stable COPD patients.

STUDY OBJECTIVE: To evaluate the short-term physiologic effects of two settings of nasal pressure-support ventilation (NPSV) in stable COPD patients with chronic hypercapnia. DESIGN: Randomized controlled physiologic study. SETTING: Lung function units and outpatient clinic of two affiliated pulmonary rehabilitation centers. PATIENTS: Twenty-three patients receiving domiciliary nocturnal NPSV for a mean (+/- SD) duration of 31 +/- 20 months. METHODS: Evaluation of arterial blood gases, breathing pattern, respiratory muscles, and dynamic intrinsic positive end-expiratory pressure (PEEPi,dyn) during both unassisted and assisted ventilation. Two settings of NPSV were randomly applied for 30 min each: (1) usual setting (U), the setting of NPSV actually used by the individual patient at home; and (2) physiologic setting (PHY), the level of inspiratory pressure support (IPS) and external positive end-expiratory pressure (PEEPe) tailored to patient according to invasive evaluation of respiratory muscular function and mechanics. RESULTS: All patients tolerated NPSV well throughout the procedure. Mean U was IPS, 16 +/- 3 cm H(2)O and PEEPe, 3.6 +/- 1.4 cm H(2)O; mean PHY was IPS, 15 +/- 3 cm H(2)O and PEEPe, 3.1 +/- 1.6 cm H(2)O. NPSV was able to significantly (p < 0.01) improve arterial blood gases independent of the setting applied. When compared with spontaneous breathing, both settings induced a significant increase in minute ventilation (p < 0.01). Both settings were able to reduce the diaphragmatic pressure-time product, but the reduction was significantly greater with PHY (by 64%; p < 0.01) than with U (56%; p < 0.05). Eleven of 23 patients (48%) with U and 7 of 23 patients (30%) with PHY showed ineffective efforts (IE); the prevalence of IE (20 +/- 39% vs 6 +/- 11% of their respiratory rate with U and PHY, respectively) was statistically different (p < 0.05). CONCLUSION: In COPD patients with chronic hypercapnia, NPSV is effective in improving arterial blood gases and in unloading inspiratory muscles independent of whether it is set on the basis of patient comfort and improvement in arterial blood gases or tailored to a patient's respiratory muscle effort and mechanics. However, setting of inspiratory assistance and PEEPe by the invasive evaluation of lung mechanics and respiratory muscle function may result in reduction in ineffective inspiratory efforts. These short-term results must be confirmed in the long-term clinical setting.

Induced sputum cellularity. Reference values and distribution in normal volunteers.

Sputum induction has recently been proposed as the only direct noninvasive method for measuring airway inflammatory indices. The reference values and the distribution of cells in induced sputum in a control population have not yet been well defined. We therefore evaluated data from a large number of healthy volunteers. One hundred fourteen healthy, nonatopic, nonsmoking volunteers without airway hyperreactivity were enrolled (age: 38 +/- 13 yr [mean +/- SD]; FEV(1): 105 +/- 10% predicted; provocative dose of methacholine inducing a 20% decrease FEV(1) > 3,200 microgram). Ninety-six subjects (84%) produced adequate analysis samples. The subjects had a normal age distribution. Their induced sputum was rich in macrophages (69.2 +/- 13%) and neutrophils (27.3 +/- 13%), and poor in eosinophils (0.6 +/- 0.8%), lymphocytes (1.0 +/- 1.2%), and epithelial cells (1.5 +/- 1.8%). Only macrophages and neutrophils showed a normal distribution; total and differential counts of other cells did not. We propose that these data be used in comparison of the induced sputum cells of normal subjects and those of patients with airway inflammation.