Bronchoalveolar pH and inflammatory biomarkers in patients with acute exacerbation of chronic obstructive pulmonary disease.

OBJECTIVES: This study aimed to directly measure pH in the lungs, determine lactate dehydrogenase (LDH), C-reactive protein (CRP), and glucose levels in serum and bronchoalveolar aspirate, and identify bacterial pathogens from bronchoalveolar fluid during acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: We performed an observational, analytical case-control study from February 2015 to March 2017. We included 84 patients with AECOPD and 42 with stable chronic obstructive pulmonary disease (COPD). All participants underwent detailed medical anamnesis, a clinical examination, chest radiography, spirometry, an arterial blood gas test, bronchoscopy, bacterial culture, and serum/bronchiolar aspirate laboratory testing. RESULTS: The mean pH of bronchoalveolar fluid was significantly higher in patients with AECOPD than in patients with stable COPD. The mean lung pH value, bronchoalveolar and serum LDH levels, and serum CRP levels in patients with isolated bacteria were higher than those in patients without isolated bacteria in the AECOPD patient group. Lung pH values in patients with AECOPD were significantly correlated with bronchoalveolar LDH and glucose levels. CONCLUSIONS: AECOPD is associated with local cell and tissue injury in the lungs, especially in the presence of bacterial pathogens, which is accompanied by a low systemic inflammatory response.

Bus water storage tank as a reservoir of Legionella pneumophila.

Health concerns associated with Legionnaires' disease have been identified as an area of the increasing public and professional interest. Any natural water or man-made water systems worldwide might be reservoirs of Legionellae. We presented a sporadic, community-acquired case of Legionnaires' disease caused by Legionellapneumophila serogroup 1 in a bus driver who used water for hand and face washing from a bus water storage tank. The history of any other usual place of exposure to Legionellae was negative. The water from the tank was dirty, filled with sediment and leaves, at the temperature of 22 degrees C. The water was heavily contaminated with Legionella pneumophila serogroup 1 isolated from each sample with the concentration of 66,000, 16,000, 42,000, 56,000 and 34,000 CFU/L. The disinfection of the bus water storage tank was made using hyperclorination with 50 mg/L of free residual chlorine. The control sampling one week after the disinfection yielded negative results. So far, there are no recommendations on regular management or disinfection of water in bus storage tanks, but it seems to be reasonable to assume that passengers as well as bus drivers may be exposed to Legionella and therefore at risk of acquiring the infection. These recommendations should include regular empting, rinsing and filling the tank with fresh tap water, at least once a week. Finally, we have to be aware that Legionella bacteria are ubiquitous and any potential mode of producing contaminated aerosol should not be overlooked during an epidemiological field investigation and proposed appropriate measures.

Bronchoalveolar pH and inflammatory biomarkers in newly diagnosed IPF and GERD patients: a case-control study.

BACKGROUND: Several studies have suggested that idiopathic pulmonary fibrosis (IPF) may be related to repeated aspiration of gastric contents over long periods of time. We aimed to investigate differences between pH measured directly in the lung, and biomarkers of acute inflammation in patients with newly diagnosed IPF and in patients with newly diagnosed GERD. MATERIAL AND METHODS: All subjects (N=61) underwent collection of medical history, physical examination, pulmonary function testing, bronchoscopy, endoscopy, arterial blood gas analyses, and biochemical testing. RESULTS: Previously diagnosed GERD was found in 56.7%, typical symptoms of reflux in 80%, and Helicobacter pylori in gastric biopsy specimens in 76.6% of the cases. pH in peripheral branches of bronchi in the cases was 5.32 ± 0.44 and was 6.27 ± 0.31 (p<0.001) in the control group. The average values of LDH, ALP, and CRP in bronchoalveolar aspirate and in serum, as well as TNF-alpha in bronchoalveolar aspirate, were significantly higher in IPF patients. CONCLUSIONS: The more acidic environment in the bronchoalveolar aspirate of the IPF subjects could contribute to the development or progression of IPF, possibly via changes in local metabolism or by damaging local cells and tissue. However, further studies with larger numbers of patients are required to clarify the role of gastric fluid aspiration in IPF pathogenesis. Our preliminary work has identified inflammatory biomarkers LDH, ALP, and TNF-alpha as potentially important in the pathologic processes in IPF. Further research is needed to determine their importance in clinical intervention and patient care.

[Delays in diagnosing and treating tuberculosis in Croatia]. / Izgubljeno vrijeme u otkrivanju i pocetku lijecenja tuberkuloze: sto treba napraviti?

The aim of this study was to determine factors causing delay in tuberculosis diagnosis and treatment in Croatia. It included 240 adults with pulmonary tuberculosis, who were interviewed for demographics, socioeconomic, lifestyle, and personal health data. Total delay was defined as a number of days from the onset of symptoms to the initiation of therapy. The median and the 75th percentile of the total delay were 68 and 120 days, respectively: 16.7 % of the patients initiated treatment within the first month, 23.8 % within the second month, 23.3 % within the third month, 12.9 % within the fourth month, and 23.3 % more than four months after the symptoms appeared. Long delay (exceeding median delay) was strongly associated with drug abuse (p=0.021). Extreme delay (75th percentile of delay) was significantly associated with the lowest level of education (p=0.021), below minimal income (p=0.039), minimal to average income (p=0.020), current smoking (p=0.050), and co-morbidity (p=0.048). In the multivariate model, long delay remained associated with drug abuse, while extreme delay was associated with the lowest level of education (p=0.033) and current (p=0.017) and ex-smoking (p=0.045).In a setting with decreasing TB incidence, the reported delay can be reduced by increasing health education, not only about tuberculosis per se, but about health in general and attitudes towards prevention and early care. It is also important to increase tuberculosis knowledge among healthcare workers as well as their diagnostic skills.

[Measurement of inspiratory flow for the selection of the inhalation treatment device for asthma and COPD]. / Mjerenje inspiracijskog protoka zraka pri odabiru oblika inhalacijskog lijeka za astmu i KOPB.

AIM: To assess the proportion of patients with asthma or chronic obstructive pulmonary disease (COPD) with significant bronchoobstruction who do not have inspiratory flows necessary for the adequate use of dry powder inhaler (DPI) devices Diskus and Turbuhaler. PATIENTS AND METHODS: multicentre cross-sectional study that included 400 patients with asthma or COPD (with FEV1 < 60%) aged 5-91 years tested during exacerbation or usual control visit. All patients underwent lung function testing and measurement of inspiratory flows using In-check Dial. RESULTS: Significantly lower proportion of patients didn't have inspiratory flows necessary for the regular adequate use of Diskus than for Turbuhaler (21.0% vs 87.0%, chi2 = 350.72, p < 0.0001). In patients tested during exacerbation these proportions were marginally greater. Regression analysis showed a weak association of inspiratory flows measured with different resistance settings with parameters of lung function (best association was seen between resistance setting for Diskus and PEF [%], r2 = 0.104). CONCLUSIONS: Significant proportion of patients with asthma or COPD with significant bronchoobstruction do not exhibit satisfactory inspiratory flows for the use of dry powder inhaler (DPI) devices (Diskus < Turbuhaler). Spirometry is not to be used for selection of the device for drug application and In-check Dial should be used instead.

The role of interferon-gamma release assay in tuberculosis control.

Tuberculosis is still one of the major global public health threats. Countries with low incidence must focus on exhausting the reservoir of future cases by preventing reactivation. Therefore, it is important to identify and effectively treat those individuals who have latent tuberculosis infection and who may develop active disease. The tuberculin skin test has been the standard for detection of immune response against M. tuberculosis since the beginning of the 20th century. The new millennium has brought advancement in the diagnosis of latent tuberculosis infection. The name of the new blood test is interferon-gamma release assay (IGRA). Croatia is a middle-incidence country with a long decreasing trend and developed tuberculosis control. To reach low incidence and finally eliminate tuberculosis, its tuberculosis programme needs a more aggressive approach that would include intensive contact investigation and treatment of persons with latent tuberculosis infection. This article discusses the current uses of IGRA and its role in tuberculosis control.

Intraregional differences in asthma prevalence and risk factors for asthma among adolescents in Split-Dalmatia County, Croatia.

BACKGROUND: Our aim was to assess the differences in intraregional prevalence of asthma in adolescents in Split-Dalmatia County to determine asthma risk factors in our population and estimate the specificity and sensitivity of the questionnaire used. MATERIAL/METHODS: We conducted the study using the European Community Respiratory Health Survey II short questionnaire supplemented by some questions from the International Study of Asthma in Childhood questionnaire. The participants suspected to have asthma were invited for examination by an asthma specialist who established the final diagnosis of asthma according to the medical history, physical examination, skin-prick tests, and peak flow measurements. RESULTS: A total of 4027 students (51.2% male) participated in the study. According to the prevalence of wheezing during the last 12 months, asthma prevalence was estimated at 9.7%. The total prevalence of asthma confirmed by an asthma specialist in the selected population was 5.60% (95% CI, 4.93-6.36%); 6.18% in Split (95% CI, 5.37-7.09), 5.63% in Imotski (95% CI, 3.48-8.58), and 2.90% in Sinj (95% CI, 1.67-4.68) (P=0.0028). We found sensitization to aeroallergens and peanuts, and active smoking to be independent risk factors for asthma. CONCLUSIONS: Split-Dalmatia County has moderate asthma prevalence, with a significant intraregional difference. Asthma prevalence estimated by a questionnaire (9.7%) overestimates the prevalence of asthma confirmed by an asthma specialist (5.6%) in adolescents in Croatia. Our data confirmed the need of a more complex questionnaire to evaluate the accurate prevalence of current asthma or the need for subsequent clinical evaluation of the questionnaire obtained data. Allergic sensitization to aeroallergens and active smoking were important risk factors for asthma.

Undiagnosed AIDS in patients with progressive dyspnoea: an occupational risk for healthcare workers in Croatia.

Pulmonary diseases are well documented and diverse in many patients with HIV in clinical stages 3 and 4. It is not unusual that these patients, most of whom do not know that they are already HIV-infected, are first examined and hospitalised by respiratory medicine specialists. While HIV-infection is relatively simple to diagnose if accompanied by advanced clinical manifestations and is regularly checked in patients with increased risk, this is not the case in low-risk patients, particularly in countries with low-level HIV epidemic and therefore low index of suspicion. Regular examination involves a series of tests, often including bronchoscopy with transbronchal lung biopsy in order to identify an interstitial lung disease and/or progressive dyspnoea. It is not uncommon that patients provide false or incomplete information about their lifestyle, which can mislead the clinician. At this point, HIV-infection is usually not suspected and healthcare workers may not strictly be following the safety principles which are otherwise applied when HIV-infection is known or suspect, although universal precautions are routine practice. At this point, the risk of exposure is the highest and HIV-transmission to healthcare workers is the most likely to occur. The cases presented here indicate that patients with progressive dyspnoea, which is typical of interstitial lung diseases, should undergo HIV-testing as a part of good clinical practice, even in a country with low-level HIV epidemic.

The influence of gastroesophageal reflux in the lung: a case-control study.

BACKGROUND AND OBJECTIVE: Many researchers have investigated the pH of exhaled breath condensate but direct measurement of pH in the lung has not been performed in vivo in humans. We hypothesized that the pH measured directly in the lung would differ between healthy subjects and patients with gastroesophageal reflux disease (GERD). We also wished to determine whether an acidic environment in the lung influences pulmonary function and DL(CO), and whether microaspiration of gastric contents directly influences non-specific inflammation in the lung. METHODS: The patients were otherwise healthy individuals who had been newly diagnosed with GERD. The control subjects were mostly volunteers who underwent bronchoscopy for different reasons. For all subjects (n = 63) a medical history was taken, and physical examination, oesophagogastroduodenoscopy, fibre-optic bronchoscopy and pulmonary function testing were performed. RESULTS: In patients with GERD the average pH in the lung was 5.13 +/- 0.43; this was significantly lower than the pH in the lung of controls 6.08 +/- 0.39 (P = 0.001). Patients with GERD had lower FEV(1)% (P = 0.035), PEF (P = 0.001), FEF(50%) (P = 0.002) and FEF(25%) (P = 0.003), while the differences in FVC% and FEF(75%) were not significant. DL(CO) (P = 0.003), as well as transfer coefficient of the lung (P = 0.001), was lower in patients with GERD. LDH levels in bronchoalveolar aspirate were higher in the patients with GERD (P = 0.001). CONCLUSIONS: This study found evidence of cell and tissue injury in the lung, a lowering of pH and higher bronchoalveolar aspirate LDH levels in patients with GERD compared with healthy subjects. These findings suggest that pulmonary function, and especially DL(CO), should be evaluated in patients presenting with GERD.

Beta2-microglobuline plasma level and painful shoulder in haemodialysed patients.

Painful shoulder in patients on chronic haemodialyis is most often associated with dialysis arthropathy or accumulation of deposits containing modified fibrils of beta2- microglobuline especially in bones and joints due to insufficient elimination during the therapy. The aim of this study is to investigate whether there is connection between painful shoulder and plasma level of beta2-microglobuline and to corroborate that with morphologic parameters found in proved amyloidosis. It has to be emphasized that even other causes may contribute the development of painful shoulder. Real time sonography and conventional plain radiographs of the 108 shoulders were performed in 54 patients receiving chronic haemodialysis as a treatment of terminal renal failure (without previous history of rheumatoid arthritis), 27 symptomatic with persistent pain and stiffness in both shoulders and lasting for more than 6 weeks and restriction of movements in various degree and 27 asymptomatic. Plasma level of beta2-microglobuline, CRP and uric acid were taken periodically as routine procedure during a one year prospective trial, as well as plasma level of calcium, phosphor and alkaline phosphatase. Plasmatic level of beta2-microglobuline is strongly connected with painful shoulder in dialyzed patients, as well as CRP as sign of acute inflammation. That is proved by morphologic parameters associated with histological proved amyloidosis in patients on long term dialysis, more then 10 years.

A rare case of pulmonary tuberculosis with simultaneous pulmonary and skin sarcoidosis: a case report.

BACKGROUND: Tuberculosis and sarcoidosis are chronic diseases that rarely occur concomitantly. Sarcoidosis is a multisystem granulomatous disorder characterized pathologically by the presence of non-caseating granulomas in involved tissues. Tuberculosis is infectious disease caused by Mycobacterium tuberculosis characterized by granulomas with caseous necrosis. CASE PRESENTATION: We present a case of 43-year-old female refugee from Kosovo with microbiological confirmation of pulmonary tuberculosis and pulmonary and skin sarcoidosis at the same time. Three weeks after corticosteroid therapy for pulmonary sarcoidosis was introduced, positive finding of mycobacterium culture of bronchial aspirate was observed. Based on these results, corticosteroid therapy was excluded and antituberculous therapy was introduced for six months. In the meantime, new nodes on face and nose appeared and skin sarcoidosis was diagnosed. The patient was given corticosteroids and colchicine according to the skin and pulmonary sarcoidosis therapy recommendation. CONCLUSION: The authors of this study suggest that in cases when there is a dilemma in diagnosis between tuberculosis and sarcoidosis we should advance with corticosteroid therapy until we have microbiological confirmation of mycobacterium culture. This case is remarkable because this is a third described case of sarcoidosis and tuberculosis together (the first reported in Asia, the second in South Africa), and to authors knowledge, this is a first case report in Europe.

Interobserver variations in diagnosing asbestosis according to the ILO classification.

Inhalation of asbestos fibres leads to asbestosis of the pleura and the lung, with possible progression to lung cancer and malignant pleural or peritoneal mesothelioma. Asbestosis remains difficult to diagnose, especially in its early stages. The most important role in its diagnosis is that of chest radiographs. The aim of this cross-sectional study was to address interobserver variations in interpreting chest radiographs in asbestos workers, which remain to be an issue, despite improvements in the International Labour Office (ILO) classification system. In our ten-year study, we investigated 318 workers occupationally exposed to asbestos, and in 210 workers with diagnosed asbestos-related changes we compared interpretations of chest radiographs according to ILO by two independent radiologists. The apparent degree of interobserver variation in classifying lung fibrosis was 26.66% for the diameter of changes and 42.2% for the profusion of the changes. In cases with diffuse pleural thickening, the interobserver variation using ILO procedures was 34.93%. This investigation raises the issue of standardisation and objectivity of interpretation of asbestosis according to the ILO classification system. This study has revealed a significant disagreement in the estimated degree of pleural and parenchymal asbestos pulmonary disease. This is why we believe high-resolution computed tomography (HRCT) should also be used as a part of international classification.

Genitourinary diseases prior spontaneous abortion as a risk factor for recurrent pregnancy loss.

The etiology of recurrent spontaneous abortion (RSA) is still unexplained. Many couples do not find the cause of their RSA at all. The purpose of this research was to evaluate the association between recurrent pregnancy loss and previous (cured prior to pregnancy) acute/chronic genitourinary infections in both parents. Couples (226) having two or more (up to six) spontaneous abortions were analyzed in this retrospective case-control study. The control group consisted of 124 couples with neither miscarriages nor complicated pregnancies in their past. The data (serum immunological markers, karyotype, flow cytometry data, PHD) were collected from their medical charts. It was found that there was no statistically significant difference in average weeks of pregnancy in which the second, third and fourth abortion occurred. There was a statistically significant difference in previously experienced genitourinary infections between women from the RSA group and the control group, as well as for men from the RSA group and the control group. It can be concluded that past infections of the maternal and/or paternal genitourinary system may be the causal factor for recurrent pregnancy loss and can also pre-determine women that are of greater susceptibility to preterm pregnancy. Therefore the genetic counseling of couples should include thorough medical and family history of both partners and their first- and second-degree relatives in conjunction with typical medical examination.

Increasing of malignant pleural mesothelioma: burning issue in Split-Dalmatian County, Croatia.

Asbestos-related diseases are one of the burning public health issues worldwide. The incidence and the epidemiological patterns of malignant pleural mesothelioma in Split-Dalmatian County, where a large part of Croatian industry related to asbestos processing and use have been situated were assessed in this study. The history of asbestos-related issues and development of current legislation in Croatia was also discussed briefly. Data on the incidence were collected retrospectively from the medical records of patients with malignant pleural mesothelioma treated at Department of Pulmonary Diseases University Hospital Split during the 2000-2007 period. A total of 137 new cases was recorded with the mean incidence of 3.55/100,000 and the trend was increasing over years compared with 1992-1995 period in the same county when the mean incidence was 1.7/100,000. Men accounted for 85.4% of all cases. The mean age of patients was 64.9 +/- 15.4 years. The majority of patients were occupationally exposed to asbestos (85.4%), 8.8% had environmental exposure, and 2.2% had domestic exposure. The type of household exposition was in 5.8% of patients. More than half of the cases were exposed to asbestos 31-40 years. The mean length of exposure was 28.87 +/- 15.63 years. The incidence of malignant pleural mesothelioma in Split-Dalmatian County has been obviously increasing due to the predominantly occupational exposure and it is reasonable to assume that it will remain high in the next two-three decades and to be a reason for concern and fear among the general population.

Removal of tracheobronchial foreign bodies in adults using flexible bronchoscopy: experience 1995-2006.

BACKGROUND: Tracheobronchial foreign body (TFB) removal in adult patients using the combined technique of flexible bronchoscopy (FBSC) through the endotracheal tube as well as using the simple FBSC has not often been described. This study reports our experience with FBSC for removal of TFBs and describes diagnosis, techniques of removal, and types of TFBs. METHODS: We retrospectively examined bronchoscopic records of adult patients performed between 1995 and 2006 and collection of foreign bodies in Clinical Department for Respiratory Diseases, University Hospital Split, Croatia. RESULTS: TFBs were found in 86 (0.33%) out of 26,124 patients who were submitted to bronchoscopy. The majority of the patients (90%) had some risk factor for aspiration, among which stroke (30%) was the most frequent. Patients with different neurologic and neuromuscular diseases together accounted for 58% of all patients with TFB aspiration. Medical history was suggestive of foreign body aspiration in 38.4% of the patients, while chest X-ray was indicative in 7% of the patients. TFBs were most often found in the right bronchial tree (75.6%). The most common TFBs were animal and fish bones (39.5%). In 90.7% of the patients they were successfully removed under FBSC, whereas in 8.1% of the patients a TFB was extracted with flexible bronchoscope through endotracheal tube. Surgery was needed in only one case. CONCLUSIONS: Although foreign bodies in the tracheobronchial tree are rare in adults, the clinician must be aware of their likelihood. Foreign body aspiration should be considered especially in the etiology of recurrent lung diseases and in the presence of risk factors for aspiration, in particular with different neurologic and neuromuscular diseases. They can be successfully and safely removed in the majority of patients under local anesthesia by using FBSC. In cases when repeated procedure is needed, endotracheal tube is recommended.

Long-term course and treatment of a cutaneous BCG infection.

The authors report and discuss a rare case of the long-term course and treatment of cutaneous BCG infection in an HIV-negative, healthy nurse. Over 5 years we cured the wrist and lower leg cutaneous tuberculosis infection caused by an accident at work. Persistent antituberculous therapy and surgical procedure were applied, but after detection of an encapsulated abscess in the wrist followed by needle aspiration, antituberculous therapy was sufficient and our patient was cured. Failing the addition of local applications, antituberculous therapy with radical surgical treatment remains the recommended treatment in cutaneous infections.

Pulmonary function in persons who are professionally exposed to formaldehyde fumes.

The present study examines long-term effects of occupational exposure to formaldehyde fumes on lung function. Forced spirometry and diffusing lung capacity were measured in 16 health-service professionals (8 medical doctors and 8 laboratory technicians) working at the pathoanatomic laboratory for at least 4 years with daily exposure 8 +/- 1 hours. Control group employed 16 males, which were matched by age and stature to members of the exposed group. Only non-smokers were included in the study. Spirometric parameters in study participants exposed to formaldehyde fumes compared to control group were not significantly different indicating absence of restrictive and/or obstructive deterioration of lung function in exposed group. The only parameter differing in two groups was blood volume of pulmonary capillaries (Vc') which was significantly larger in a group exposed to formaldehyde fumes. The possibility that the hyperemic lung reaction is the consequence of the exposure to formaldehyde fumes should be further explored.

Lung function changes in pleural asbestosis.

The aim of this study was to examine the relationship between radiographically detectable pleural changes and lung function in pleural asbestosis. One hundred and twenty chrysotile asbestos-exposed workers were enrolled in this retrospective study. For each examinee the length of asbestos exposure and the degree of dust cover at the workplace were assessed as well as the radiological and functional tests has been performed. The examinees were divided into two groups based on radiologically detectable changes: a) group with pleural changes (29%) and b) group without perceived pleural changes (71%). The obtained results indicate association between the length of asbestos exposure, pleural changes and the impairment of lung function.