Saliva as a non-invasive specimen for COPD assessment.

BACKGROUND: People with COPD have been reported to bear a distinct airway microbiota from healthy individuals based on bronchoalveolar lavage (BAL) and sputum samples. Unfortunately, the collection of these samples involves relatively invasive procedures and is resource-demanding, limiting its regular use. Non-invasive samples from the upper airways could constitute an interesting alternative, but its relationship with COPD is still underexplored. We examined the merits of saliva to identify the typical profile of COPD oral bacteria and test its association with the disease. METHODS: Outpatients with COPD and age-sex matched healthy controls were recruited and characterised based on clinical parameters and 16S rRNA profiling of oral bacteria. A clustering analysis based on patients' oral bacteria beta-diversity and logistic regressions were performed to evaluate the association between oral bacteria composition and COPD. RESULTS: 128 individuals participated (70 patients and 58 controls). Differential abundance analyses showed differences in patients comparable to the ones previously observed in samples from the lower respiratory tract, i.e., an increase in Proteobacteria (particularly Haemophilus) and loss of microbiota diversity. An unsupervised clustering analysis separated patients in two groups based on microbiota composition differing significantly in the frequency of patients hospitalized due to severe acute exacerbation of COPD (AECOPD) and in the frequency of GOLD D patients. Furthermore, a low frequency of Prevotella was associated with a significantly higher risk of recent severe AECOPD and of being GOLD D. CONCLUSION: Salivary bacteria showed an association with COPD, particularly with severe exacerbations, supporting the use of this non-invasive specimen for future studies of heterogeneous respiratory diseases like COPD.

Bacterial lysates (OM-85 BV): a cost-effective proposal in order to contrast antibiotic resistance.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is one of the most frequent pathologies in which antibiotics are used because 50% of the exacerbations are attributable to a bacterial infection. The aims of our study were: i) to perform a meta-analysis on the efficacy of the bacterial lysate OM-85 BV in preventing acute exacerbations in patients with COPD; ii) to evaluate whether this preventive treatment can lead to significant savings for the National Health Service (NHS). METHODS: A systematic research was conducted in the electronic database MEDLINE (PubMed) in June 2017-July 2020, collecting evidences without time restrictions. Only randomized controlled trials (RCTs) were included. The keywords used were "OM 85 BV AND chronic bronchitis" and "OM 85 BV AND COPD". A cost-effectiveness analysis (CEA) was performed considering the costs for a treatment with OM-8BV, the costs for the treatment of an acute exacerbation and the number of prevented exacerbations. RESULTS: 59 publications were found, but the meta-analysis was conducted on 13 studies that met the inclusion criteria. OM-85 BV is responsible of a statistically significant reduction in the mean number of COPD exacerbations (p < 0.01; WMD = -0.86; CI 95%: -1.38, -0.34) and in the days of antibiotic therapy (p < 0.01; WMD = -9.49; CI 95%: -11.93, -7.05). The cost-effectiveness ratio with a negative value is in favor to treatment. CONCLUSIONS: OM-85 BV is effective in reducing exacerbations, and could lead to significant savings for the NHS. Moreover, reducing the number of exacerbations it could avoid an over-use of antibiotics and the consequent antibiotic resistance.

Comparative effectiveness of pneumococcal vaccination with PPV23 and PCV13 in COPD patients over a 5-year follow-up cohort study.

Vaccination against Streptococcus pneumoniae is among the most effective measures for preventing pneumonia and reducing the rate of chronic obstructive pulmonary disease (COPD) exacerbations. The objective of this work was to evaluate the long-term effectiveness of PCV13 and PPV23 for preventing pneumonia and COPD exacerbations. The open-label, prospective, observational cohort study involved 302 male patients aged ≥ 45 years: PCV13 group (n = 123); PPV23 group (n = 32); and vaccine-naïve group (n = 147). The primary endpoint included the frequency of pneumonia episodes and COPD exacerbations per year over a 5-year follow-up period. The secondary endpoints included the dynamics of dyspnea severity (MMRC), the BODE index, FEV1, the CAT index, the SGRQ score, and the results of 6-min walk test. Vaccination with PCV13 and PPV23 significantly reduces the total rate of pneumonia during the first year after vaccination. Starting with the second year, clinical effectiveness in PPV23 group decreases compared with both PCV13 group and vaccine-naïve patients. Pneumonia by year 5 after vaccination was registered in 47% of patients in the PPV23 group, versus 3.3% of patients in the PCV13 group (p < 0.001); COPD exacerbations-in 81.3% versus 23.6%, respectively (p < 0.001). Vaccination with PCV13 significantly reduced and maintained the BODE index over the 5-year follow-up period. Although both vaccines have comparable clinical effects during the first year after vaccination, only PCV13 is characterized by persistent clinical effectiveness during the 5-year follow-up period. Patients older than 55 years who received PPV23 have significantly higher risks of having pneumonia episodes more frequently during the long-term follow-up.

Assessment of bacterial exposure on phagocytic capability and surface marker expression of sputum macrophages and neutrophils in COPD patients.

Defective phagocytosis has been shown in chronic obstructive pulmonary disease (COPD) bronchoalveolar lavage and blood monocyte-derived macrophages. Phagocytic capabilities of sputum macrophages and neutrophils in COPD are unknown. We investigated phagocytosis in these cells from COPD patients and controls. Phagocytosis of Streptococcus pneumoniae or fluorescently labelled non-typeable Haemophilus influenzae (NTHi) by sputum macrophages and neutrophils was determined by gentamycin protection assay (COPD; n = 5) or flow cytometry in 14 COPD patients, 8 healthy smokers (HS) and 9 healthy never-smokers (HNS). Sputum macrophages and neutrophils were differentiated by adherence for the gentamycin protection assay or receptor expression (CD206 and CD66b, respectively), by flow cytometry. The effects of NTHi on macrophage expression of CD206 and CD14 and neutrophil expression of CD16 were determined by flow cytometry. There was greater uptake of S. pneumoniae [~10-fold more colony-forming units (CFU)/ml] by sputum neutrophils compared to macrophages in COPD patients. Flow cytometry showed greater NTHi uptake by neutrophils compared to macrophages in COPD (67 versus 38%, respectively) and HS (61 versus 31%, respectively). NTHi uptake by macrophages was lower in HS (31%, p = 0.019) and COPD patients (38%, p = 0.069) compared to HNS (57%). NTHi uptake by neutrophils was similar between groups. NTHi exposure reduced CD206 and CD14 expression on macrophages and CD16 expression on neutrophils. Sputum neutrophils showed more phagocytic activity than macrophages. There was some evidence that bacterial phagocytosis was impaired in HS sputum macrophages, but no impairment of neutrophils was observed in HS or COPD patients. These results highlight the relative contributions of neutrophils and macrophages to bacterial clearance in COPD.

Infection of Mycobacterium tuberculosis Promotes Both M1/M2 Polarization and MMP Production in Cigarette Smoke-Exposed Macrophages.

Pulmonary tuberculosis (PTB) is a risk factor for COPD. Our previous study revealed more severe emphysema in COPD patients (mostly smokers) with prior tuberculosis. However, the mechanisms of interactions between cigarette smoke (CS) and Mycobacterium tuberculosis (Mtb) are unknown. In this study, we found that the frequencies of both M1 and M2 macrophages, and levels of MMP9 and MMP12 in bronchoalveolar lavage were increased in PTB patients with smoking. Between-group analysis showed that the frequency of M1 macrophages was higher in non-smoker PTB patients while more M2 macrophages were found in smokers without PTB, as compared to the non-smoker healthy controls. Bacille Calmette-Guérin (BCG) infection in CS extract (CSE)-incubated MH-S cells further enhanced secretion of M1-related (iNOS, IFN-γ and TNF-α) and M2-related (TGF-ß and IL-10) cytokines, reactive oxygen species (ROS) production and cellular apoptosis, concomitantly with up-regulation of MMP9 and MMP12, but not TIMP1. Moreover, BCG infection in acutely CS-exposed mice promoted macrophage polarization toward both M1 and M2 phenotypes, along with increased lung inflammatory infiltration. MMP9 and MMP12, but not TIMP1, were further up-regulated in lung tissues and BAL fluid after BCG infection in this model. Taken together, Mtb Infection promoted CS-exposed macrophages to polarize toward both M1 and M2 phenotypes, along with enhanced production of MMP9 and MMP12. These findings provide insights into the mechanistic interplay between CS exposure and tuberculosis in the pathogenesis of COPD.

A time for everything and everything in its time - exploring the mechanisms underlying seasonality of COPD exacerbations.

Across Europe, COPD affects 23 million people leading to annual health care costs of ~€25.1 billion. This burden is particularly severe during winter months in association with the peak incidence of exacerbation events. Seasonal variation in the health status of patients with COPD places additional and often critical pressure on already strained health care resources. COPD exacerbations are characterized by worsening day-to-day symptoms of an individual and often triggered by respiratory infections, but the process by which this occurs in a seasonal fashion is likely to be multifactorial. In this review, we discuss recent population studies that highlight the impact of seasonality in COPD and review the proposed biological mechanisms underlying this. An appraisal of the role of the host susceptibility and response, environmental triggers and the biology of respiratory pathogens is detailed. The impact of each aspect is considered, and an integrated model of the context for the whole individual and society in general is explored.

Nontuberculous mycobacterial disease managed within UK primary care, 2006-2016.

Previous UK studies investigating nontuberculous mycobacteria have been limited to reporting isolation from culture, not burden of disease. We assessed the burden of nontuberculous mycobacterial disease (NTMD) in UK primary care from 2006 to 2016. Using electronic healthcare records, we identified patients with NTMD using a strict definition including patients with guideline-directed treatment/monitoring. We described treatment regimens and incidence/prevalence in the general population and in patients with underlying chronic respiratory diseases. Incidence of primary care-managed NTMD in the general population decreased (2006 to 2016 rates per 100,000 person-years, 3.85 to 1.28). Average annual prevalence of NTMD in the general population was 6.38 per 100,000. Around 85% were taking antimycobacterial therapy; 53.2% were taking a guideline-recommended regimen. Incidence of NTMD in patients with respiratory disease decreased (2006 to 2016 rates per 100,000 person-years, 12.5 to 7.40). Average annual prevalence of NTMD in patients with respiratory disease was 27.7 per 100,000. This is the first UK study using nationally representative data to investigate the burden of NTMD managed within primary care. Incidence and prevalence of managed NTMD within primary care is gradually declining. Increasing complexity in the management of NTMD may be driving a shift in care to secondary settings.

General practitioner use of a C-reactive protein point-of-care test to help target antibiotic prescribing in patients with acute exacerbations of chronic obstructive pulmonary disease (the PACE study): study protocol for a randomised controlled trial.

BACKGROUND: Most patients presenting with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in primary care are prescribed an antibiotic, which may not always be appropriate and may cause harm. C-reactive protein (CRP) is an acute-phase biomarker that can be rapidly measured at the point of care and may predict benefit from antibiotic treatment in AECOPD. It is not clear whether the addition of a CRP point-of-care test (POCT) to clinical assessment leads to a reduction in antibiotic consumption without having a negative impact on COPD health status. METHODS/DESIGN: This is a multicentre, individually randomised controlled trial (RCT) aiming to include 650 participants with a diagnosis of AECOPD in primary care. Participants will be randomised to be managed according to usual care (control) or with the addition of a CRP POCT to guide antibiotic prescribing. Antibiotic consumption for AECOPD within 4 weeks post randomisation and COPD health status (total score) measured by the Clinical COPD Questionnaire (CCQ) at 2 weeks post randomisation will be co-primary outcomes. Primary analysis (by intention-to-treat) will determine differences in antibiotic consumption for superiority and COPD health status for non-inferiority. Secondary outcomes include: COPD health status, CCQ domain scores, use of other COPD treatments (weeks 1, 2 and 4), EQ-5D utility scores (weeks 1, 2 and 4 and month 6), disease-specific, health-related quality of life (HRQoL) at 6 months, all-cause antibiotic consumption (antibiotic use for any condition) during first 4 weeks post randomisation, total antibiotic consumption (number of days during first 4 weeks of antibiotic consumed for AECOPD/any reason), antibiotic prescribing at the index consultation and during following 4 weeks, adverse effects over the first 4 weeks, incidence of pneumonia (weeks 4 and 6 months), health care resource use and cost comparison over the 6 months following randomisation. Prevalence and resistance profiles of bacteria will be assessed using throat and sputum samples collected at baseline and 4-week follow-up. A health economic evaluation and qualitative process evaluation will be carried out. DISCUSSION: If shown to be effective (i.e. leads to a reduction in antibiotic use with no worse COPD health status), the use of the CRP POCT could lead to better outcomes for patients with AECOPD and help reduce selective pressures driving the development of antimicrobial resistance. PACE will be one of the first studies to evaluate the cost-effectiveness of a POCT biomarker to guide clinical decision-making in primary care on patient-reported outcomes, antibiotic prescribing and antibiotic resistance for AECOPD. TRIAL REGISTRATION: ISRCTN registry, ID: ISRCTN24346473 . Registered on 20 August 2014.

A Moraxella catarrhalis vaccine to protect against otitis media and exacerbations of COPD: An update on current progress and challenges.

Moraxella catarrhalis is a major cause of morbidity and mortality worldwide, especially causing otitis media in young children and exacerbations of chronic obstructive pulmonary disease in adults. This pathogen uses several virulence mechanisms to colonize and survive in its host, including adherence and invasion of host cells, formation of polymicrobial biofilms with other bacterial pathogens, and production of ß-lactamase. Given the global impact of otitis media and COPD, an effective vaccine to prevent M. catarrhalis infection would have a huge impact on the quality of life in both patient populations by preventing disease, thus reducing morbidity and health care costs. A number of promising vaccine antigens have been identified for M. catarrhalis. The development of improved animal models of M. catarrhalis disease and identification of a correlate of protection are needed to accelerate vaccine development. This review will discuss the current state of M. catarrhalis vaccine development, and the challenges that must be addressed to succeed.

Mathematical modeling of postcoinfection with influenza A virus and Streptococcus pneumoniae, with implications for pneumonia and COPD-risk assessment.

BACKGROUND: The interaction between influenza and pneumococcus is important for understanding how coinfection may exacerbate pneumonia. Secondary pneumococcal pneumonia associated with influenza infection is more likely to increase respiratory morbidity and mortality. This study aimed to assess exacerbated inflammatory effects posed by secondary pneumococcal pneumonia, given prior influenza infection. MATERIALS AND METHODS: A well-derived mathematical within-host dynamic model of coinfection with influenza A virus and Streptococcus pneumoniae (SP) integrated with dose-response relationships composed of previously published mouse experimental data and clinical studies was implemented to study potentially exacerbated inflammatory responses in pneumonia based on a probabilistic approach. RESULTS: We found that TNFα is likely to be the most sensitive biomarker reflecting inflammatory response during coinfection among three explored cytokines. We showed that the worst inflammatory effects would occur at day 7 SP coinfection, with risk probability of 50% (likely) to develop severe inflammatory responses. Our model also showed that the day of secondary SP infection had much more impact on the severity of inflammatory responses in pneumonia compared to the effects caused by initial virus titers and bacteria loads. CONCLUSION: People and health care workers should be wary of secondary SP infection on day 7 post-influenza infection for prompt and proper control-measure implementation. Our quantitative risk-assessment framework can provide new insights into improvements in respiratory health especially, predominantly due to chronic obstructive pulmonary disease (COPD).

Neutrophil CD64 as a Marker of Bacterial Infection in Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are responsible for most mortality in patients with chronic obstructive pulmonary disease (COPD) and are caused mainly by bacterial infection. We analyzed and compared neutrophil CD64 expression (using the ratio of CD64 level in neutrophils to that in lymphocytes as an index), serum C-reactive protein (CRP), procalcitonin (PCT) levels, white blood cell (WBC) count, and neutrophil percentage among healthy subjects and patients with stable COPD or AECOPD. Compared with patients with COPD and healthy subjects, patients with AECOPD demonstrated significantly increased CD64 index, CRP, PCT, WBC count, and neutrophil percentage. Interestingly, CD64 index and PCT were both significantly higher in patients with AECOPD with positive bacterial sputum culture than those with negative culture. Furthermore, CD64 index and PCT were positively correlated in AECOPD, and there was also correlation between CD64 index and CRP, WBC, and neutrophil percentage. These data suggest that CD64 index is a relevant marker of bacterial infection in AECOPD. We divided patients with AECOPD into CD64-guided group and conventional treatment group. In CD64-guided group, clinicians prescribed antibiotics based on CD64 index; while in the conventional treatment group, clinicians relied on experience and clinical symptoms to determine the necessity for antibiotics. We found that the efficacy of antibiotic treatment in CD64-guided group was significantly improved compared with the conventional treatment group, including reduction of hospital stays and cost and shortened antibiotic treatment duration. Thus, the CD64 index has important diagnostic and therapeutic implications for antibiotic treatment of patients with AECOPD.

Respiratory infectious phenotypes in acute exacerbation of COPD: an aid to length of stay and COPD Assessment Test.

PURPOSE: To investigate the respiratory infectious phenotypes and their impact on length of stay (LOS) and the COPD Assessment Test (CAT) Scale in acute exacerbation of COPD (AECOPD). PATIENTS AND METHODS: We categorized 81 eligible patients into bacterial infection, viral infection, coinfection, and non-infectious groups. The respiratory virus examination was determined by a liquid bead array xTAG Respiratory Virus Panel in pharyngeal swabs, while bacterial infection was studied by conventional sputum culture. LOS and CAT as well as demographic information were recorded. RESULTS: Viruses were detected in 38 subjects, bacteria in 17, and of these, seven had both. Influenza virus was the most frequently isolated virus, followed by enterovirus/rhinovirus, coronavirus, bocavirus, metapneumovirus, parainfluenza virus types 1, 2, 3, and 4, and respiratory syncytial virus. Bacteriologic analyses of sputum showed that Pseudomonas aeruginosa was the most common bacteria, followed by Acinetobacter baumannii, Klebsiella, Escherichia coli, and Streptococcus pneumoniae. The longest LOS and the highest CAT score were detected in coinfection group. CAT score was positively correlated with LOS. CONCLUSION: Respiratory infection is a common causative agent of exacerbations in COPD. Respiratory coinfection is likely to be a determinant of more severe acute exacerbations with longer LOS. CAT score may be a predictor of longer LOS in AECOPD.

Burden of serious fungal diseases in Hungary.

Valid data on the prevalence of serious fungal diseases are difficult to derive as in most countries these conditions are not reportable infections. To assess the burden of these infections in Hungary prevalence estimates from international peer-reviewed papers and population statistics were utilised. In the intensive care unit (ICU) population at least 370 cases of serious yeast and 52 mould infections can be expected yearly. The total number of candidaemia cases may be as high as 1110 annually. In patients with acute leukaemia and recipients of haematopoietic stem cell and solid organ transplants the predicted incidence is more than 55 every year. Recurrent vulvovaginal candidiasis--though not a life-threatening condition--can adversely affect the quality of life of more than 177,000 Hungarian women. According to organisation for economic co-operation and development (OECD), 4.7% of total population older than 15 will suffer from chronic obstructive pulmonary disease (COPD) and 4.4% from asthma, adding another very broad risk group to the aforementioned categories susceptible for mycotic complications. Here more than 17,000 can have severe asthma with fungal sensitisation (SAFS) and more than 13,000 are at risk for developing allergic bronchopulmonary aspergillosis (ABPA). The incidence of dermatomycoses and other superficial fungal infections is even more difficult to assess but--according to international estimations--can affect around 14.3% of the total population. More than 1.6 million Hungarians may suffer from fungal diseases annually, with 33,000 cases being life threatening or very serious. This is an under-recognised problem of special importance for public health.

Burden of serious fungal infections in Nepal.

There are few reports of serious fungal infections in Nepal though the pathogenic and allergenic fungi including Aspergillus species are common in the atmosphere. Herein, we estimate the burden of serious fungal infections in Nepal. All published papers reporting fungal infection rates from Nepal were identified. When few data existed, we used specific populations at risk and fungal infection frequencies in those populations to estimate national incidence or prevalence. Of the 27.3 M population, about 1.87% was estimated to suffer from serious fungal infections annually. We estimated the incidence of fungal keratitis at 73 per 100,000 annually. Chronic obstructive pulmonary disease is common with 215,765 cases, contributing to 1119 cases of invasive aspergillosis annually. Of 381,822 adult asthma cases, we estimated 9546 patients (range 2673-13,364) develop allergic bronchopulmonary aspergillosis and 12,600 have severe asthma with fungal sensitisation. Based on 26,219 cases of pulmonary tuberculosis, the annual incidence of new chronic pulmonary aspergillosis (CPA) cases was estimated at 1678 with a 5 year period prevalence of 5289, 80% of CPA cases. Of 22,994 HIV patients with CD4 counts <350 not on antiretrovirals, Pneumocystis pneumonia was estimated at 990 cases annually. Cases of oral and oesophageal candidiasis in HIV/AIDS patients were estimated at 10,347 and 2950, respectively. There is a significant burden of serious fungal infections in Nepal. Epidemiological studies are necessary to validate these estimates.

Burden of serious fungal infections in Ukraine.

Ukraine has high rates of TB, AIDS and cancer. We estimated the burden of fungal disease from epidemiology papers and specific populations at risk and fungal infection frequencies. HIV/AIDS cases and deaths (2012) and tuberculosis statistics were obtained from the State Service of Ukraine, while chronic obstructive pulmonary disease (COPD) cases were from M. Miravitlles et al., Thorax 64, 863-868 (2009). Annual estimates are 893,579 Ukrainian women get recurrent vaginal thrush (≥4× per year), 50,847 cases of oral candidiasis and 13,727 cases of oesophageal candidiasis in HIV, and 101 (1%) of 10,085 new AIDS cases develop cryptococcal meningitis, 6152 cases of Pneumocystis pneumonia (13.5 cases per 100,000). Of the 29,265 cases of active respiratory TB in 2012, it is estimated that 2881 new cases of chronic pulmonary aspergillosis (CPA) occurred and that the 5-year period prevalence is 7724 cases with a total CPA burden of 10,054 cases. Assuming adult asthma prevalence is ~2.9%, 28,447 patients with allergic bronchopulmonary aspergillosis (ABPA) are likely and 37,491 with severe asthma with fungal sensitisation. We estimate 2278 cases and 376 postsurgical intra-abdominal Candida infections. Invasive aspergillosis in immunocompromised patients is estimated at 303 patients annually; 930 cases in COPD patients. Ninety cases of mucormycosis (2 per 1,000,000) are estimated. In total, ~1,000,000 (2.2%) people in Ukraine develop serious fungal infections annually.

Inhaled antimicrobial therapy - barriers to effective treatment.

Inhaled antibiotics dramatically improve targeting of drug to the site of respiratory infections, while simultaneously minimizing systemic exposure and associated toxicity. The high local concentrations of antibiotic may enable more effective treatment of multi-drug resistant pathogens. This review explores barriers to effective treatment with inhaled antibiotics. In addition, potential opportunities for improvements in treatment are reviewed.

Relationship between the GOLD combined COPD assessment staging system and bacterial isolation.

BACKGROUND: Acute exacerbations, which are a significant cause of mortality and morbidity, adversely affect chronic obstructive pulmonary disease (COPD) prognosis by accelerating loss of lung function. It is important to know the microorganisms that commonly cause exacerbations in the patient groups classified according to clinical and functional characteristics for fast and accurate treatment of acute exacerbations. OBJECTIVES: The last Global Initiative for Chronic Obstructive Lung Disease (GOLD) publication recommended a new staging system containing obstruction degree, frequency of exacerbations, and quality of life questionnaires. This study is designed to analyze the relationship between the bacteria isolated in acute exacerbations and new GOLD stages. METHODS: Potentially pathogenic bacteria (PPB) isolation with culture and polymerase chain reaction methods were obtained from 114 acute exacerbation COPD patients, classified into A, B, C, and D groups by analyzing the forced expiratory volume in 1 second (FEV1) value, COPD Assessment Test (CAT) score, and exacerbation frequency according to the new GOLD staging system. RESULTS: There was a significant correlation between exacerbation frequency and PPB isolation (P=0.002). There was no relationship between GOLD stage, FEV1, and CAT score with PPB isolation. The isolated bacteria diversity and mixed infection frequency were higher in the GOLD stage D group. Pseudomonas aeruginosa, Escherichia coli, and Acinetobacter baumannii were isolated only from D group patients. CONCLUSION: Bacterial infection may cause an acute exacerbation equally in each stage for COPD. The difference in bacterial etiology is more related to exacerbation frequency than FEV1 and CAT scores for an acute exacerbation. Determining exacerbation frequency is significant for treatment success in empirical antibiotic selection.

[Infectious exacerbation of chronic obstructive pulmonary disease: prospects for high-dose levofloxacin therapy].

This open comparative randomized study of efficacy, safety, and pharmacoeconomic characteristics of hilifox-750 (750 mg daily for 5 days) and amoxiclav 2X (875/125 mg twice daily for 10 days) included 60 patients with chronic obstructive pulmonary disease (COPD). Duration of the study was 6 months. Medians of age and smoking index in the group treated with hilifox-750 were 63.5 yr (59, 67) and 30 packs/yr (15, 60) respectively. The treatment reduced cough, apnea, sputum volume and pyoptysis with comparative rates of normalization of body temperature and peripheral leukocyte counts in both groups. Helifox-750 promoted decrease in coughing and apnea within the first three days of therapy. 28 (93%) and 26 (87%) patients recovered by day 4 of helifox and amoxiclav therapy (F-test p = 0.67). Both drugs showed comparable bacteriological efficacy. They were not different in terms of side effect frequency that were mild, resolved spontaneously and did not require withdrawal of therapy. Helifox had advantages over amoxiclav in that it reduced duration of antibacterial therapy to 5 days and of temporary incapacity to 12 days (vs 14); moreover, it needs to be taken only once daily.