Adv. Respir. Med., Volume 81, Issue 4 (June 2013) – 13 articles , Pages 283-412

Diagnozowanie gruźlicy oparte na bakteryjnym czynniku etiologicznym ma już ponad 100-letnią historię. Nowoczesna terapia rozpoczęła się jednak dopiero po II wojnie światowej wraz z odkryciem i wprowadzeniem do terapii leków przeciwprątkowych. Przez dziesięciolecia grupy międzynarodowych specjalistów pracowały nad ustaleniem najskuteczniejszych schematów leczenia [...] Full article

Zespół antyfosfolipidowy (APS) charakteryzuje się występowaniem przeciwciał antyfosfolipidowych oraz związanych z nimi zmiennych objawów klinicznych będących wynikiem zakrzepicy żylnej lub tętniczej. Podczas gdy zator w obrębie naczyń płucnych (wtórny do zakrzepicy żył głębokich) jest częstym i znanym zaburzeniem w przebiegu APS, ostatnio rośnie liczba doniesień opisujących niezakrzepowe patologie w płucach w jego przebiegu. W pracy przedstawiono przypadek młodego chorego na APS, u którego jedyną manifestacją zespołu było rozlane krwawienie pęcherzykowe. Full article

Legionella pneumophila is an agent also well known to be frequently responsible for severe community acquired pneumonia. Recent studies regarding severe community-acquired pneumonia have shown that Legionella pneumophila is the second most common cause of admission to ICU, not far behind pneumococcal pneumonia. The mortality of severe Legionella pneumonia is high (30%). We report two cases of severe respiratory failure due to Legionella pneumophila type 1 treated with non-invasive ventilation in the Respiratory Intermediate Care Unit of a Department of Respiratory Medicine with good outcomes. Severe community-acquired pneumonia is the most common cause of ARDS, and it is the primary reason for Intensive Care Unit admission with invasive mechanical ventilation. Delay in ICU admission is probably associated with a poorer outcome. The use of non-invasive ventilation in severe community acquired pneumonia is controversial. However, after recent pandemics, the number of studies reporting good rates of success for NIV has increased. Both our patients were managed in a respiratory intermediate care unit, avoiding invasive ventilation and invasive monitoring, which lowered costs yet was equally effective in providing a good outcome when compared to intubation in the Intensive Care Unit. Full article

Pulmonary hypertension (PH) is a common complication of advanced chronic obstructive pulmonary disease (COPD) and is defined by a mean pulmonary artery pressure (PAP) ≥ 25 mm Hg at rest in the supine position. Owing to its frequency, COPD is a common cause of PH; in fact, it is the second most frequent cause of PH, just after left heart diseases. PH is due to the elevation of pulmonary vascular resistance, which is caused by functional and morphological factors, chronic alveolar hypoxia being the most important. In COPD PH is generally mild to moderate, PAP usually ranging between 25 and 35 mm Hg in a stable state of the disease. A small proportion of COPD patients may present a severe or “disproportionate” PH with a resting PAP > 35–40 mm Hg. The prognosis is particularly poor in these patients. In COPD PH worsens during exercise, sleep and severe exacerbations of the disease, and these acute increases in afterload may favour the development of right heart failure. The diagnosis of PH relies on Doppler echocardiography, and right heart catheterization is needed in a minority of patients. Treatment of PH in COPD relies on long-term oxygen therapy (≥16 h/day) which generally stabilizes or at least attenuates the progression of PH. Vasodilator drugs, which are commonly used in idiopathic pulmonary arterial hypertension, have rarely been used in COPD, and we lack studies in this field. Patients with severe PH should be referred to a specialist PH centre where the possibility of inclusion in a controlled clinical trial should be considered. Full article

Nieinwazyjna wentylacja mechaniczna (NIV) jest nowoczesną metodą leczenia przewlekłej niewydolności oddychania (CRF). Wraz z rozwojem medycyny oraz społeczeństwa określanego mianem “zachodniego” wzrasta liczba osób w podeszłym wieku, u których występuje kilka chorób przewlekłych mogących współistnieć, między innymi przewlekła obturacyjna choroba płuc (POChP). W populacji dorosłych pacjentów NIV znajduje zastosowanie w leczeniu chorób nerwowo-mięśniowych, między innymi stwardnienia zanikowego bocznego (ALS) czy rdzeniowego zaniku mięśni. Do pozostałych podstawowych wskazań należą choroby restrykcyjne (wśród nich kifoskolioza), choroby płuc (głównie POChP) oraz zespół bezdechu centralnego i zespół hipowentylacji osób otyłych (OHS). W poszczególnych wskazaniach, u różnych chorych, tryb i intensywność wentylacji mogą się istotnie różnić. Celem niniejszego opracowania jest upowszechnienie wiedzy na temat roli NIV w CRF u osób dorosłych. W pracy podjęto próbę syntezy aktualnej wiedzy na temat NIV. Zwrócono również uwagę na potencjalne patomechanizmy CRF w aspekcie NIV, które powinny stać się tematem przyszłych badań naukowych. Full article

Introduction: Inherited alpha-1 antitrypsin (AAT) deficiency is one of the three most common genetic disorders in Caucasians. It considerably increases the risk of progressive obstructive lung diseases, mostly chronic obstructive pulmonary disease. It has also been suggested that AAT deficiency might be instrumental vasculitis associated with the anti-neutrophil cytoplasm antibodies (cANCA) and subsequent lung tissue injury. Material and Methods: We present the results from a pilot study involving 51 patients with granulomatosis with polyangiitis, formerly known as Wegener’s granulomatosis (GPA), 43 of whom were cANCA positive. The control group consisted of 658 individuals. AAT blood concentration assessment by nephelometry, phenotyping by isoelectrofocusing and real-time PCR genotyping were performed. Results: Deficiency alleles PI*Z and PI*S were detected in 3 (5.88%) and in 2 patients (3.92%) with GPA, respectively. All of them were cANCA positive. In the controls, PI*Z was observed in 2.8% while PI*S in 1.5% of cases. Accordingly, the increased incidence of main deficiency alleles was demonstrated in GPA, and particularly in cANCA⁺GPA patients, when compared to the controls. The estimated frequency for PI*Z in GPA, cANCA⁺GPA patients and controls was, respectively, 29.4/1000, 34.9/1000 and 13.7/1000, whereas for PI*S it was 19.2/1000, 23.2/10,00 and 7.6/1000. However, the observed differences did not reach statistical significance due to the considerable size disproportion between groups. Consclusions: We believe that our preliminary data confirm the clinical importance of AAT deficiency in GPA patients and the need to screen for AAT deficiency alleles. The study is on-going. Full article

Introduction: Recent studies have shown an increased risk of lung cancer in patients with bronchial obstructive changes, including patients with COPD. It seems that there are common factors of pathogenesis of both diseases associated with oxidative stress. In the present paper the genes linked to the repair of oxidative damage of DNA, associated with cancer, of iron metabolism and coding proteolytic enzymes were assessed. Material and Methods: The study was conducted in two groups of patients: 53 patients with non-small cell lung cancer and chronic obstructive pulmonary disease, and 54 patients only with chronic obstructive pulmonary disease. The polymorphisms of the single nucleotide were determined in the case of the majority of genes using the PCR-RFLP method. The statistical analysis of quantitative variables was executed using the Mann-Withney U-test and the test of medians; the analysis of genetic variables was executed using the χ² test. Results: Regarding the polymorphisms of genes involved in iron metabolism, statistically significant differences between the two groups have been demonstrated only in the case of haptoglobin gene HP1/2. A higher incidence of form 1/1 was found in patients with COPD and a higher incidence of form 1/2 in patients with lung cancer and COPD. Analysis of gene polymorphisms of proteolytic enzymes and inhibitors of the enzyme gene showed statistically significant differences between the two groups only for the MMP3 gene 6A/5A. In the case of the MMP12 gene polymorphism (A-82G) a tendency toward differences in the occurrence of specific alleles was identified. Conclusions: These results indicate that patients with coincidence of COPD and lung cancer have disorders of the genes involved in iron metabolism, and they have different genetic polymorphisms of proteolytic enzymes comparing to COPD patients. Full article

Introduction: A major role in the development of resistance of Mycobacterium tuberculosis to isoniazid (INH) is attributed to mutations in the katG gene coding for the catalase/peroxidase, an enzyme required for obtaining a pharmacologically active form of the drug. Analysis of mutations in the katG gene in M. tuberculosis strains may contribute to the development of reliable and rapid tests for detection of INH resistance. The aim of the study was to identify and characterize mutations in the katG gene in multidrug-resistant M. tuberculosis clinical isolates. Material and Methods: The study included 46 strains of M. tuberculosis, recovered from MDR-TB patients in Poland in 2004. Mutations in the katG gene were detected by comparing DNA sequences with the corresponding sequence of a wild-type reference laboratory strain (M. tuberculosis H37Rv). The obtained results were interpreted in the context of MIC values of INH and catalase activity of the strains tested. Results: A total of 43 (93%) strains contained mutations in the katG gene. The most frequently observed were mutations at codon 315, found in 34 (74%) strains. Mutations at other codons were rare: 4 strains contained mutations at codon 463, 2 at codon 131 and another 2 at codon 234. Mutations at codons 68, 91, 101, 126, 128 and 194 were found in single strains only. Two strains, for which no mutations at codon 315 of the katG gene were identified, had a unique translation termination mutation, which would invariably result in polypeptide truncation leading to the generation of dysfunctional catalase polypeptides. Both these strains presented the highest MIC values for INH (80 and 100 μg/mL) and showed a complete loss of catalase activity. For the remaining 41 strains with katG mutations, the MICs of INH were within the range 0.2–10 μg/mL. Thirty-six (88%) of those strains retained their catalase activity. Conclusions: Mutations at codon 315 within the katG gene, depending on their type might be useful for the prediction of INH resistance. Whereas the missense mutations do not affect the catalase activity or the level of INH resistance, the nonsense mutations result in high-level resistance to INH and a total loss of catalase activity. Full article

Introduction: HER2 (ErbB2/neu) is a member of the ErbB family of four structurally related receptors of tyrosine kinase activity. Overexpression of ErbB-1 (EGFR) and HER2 is found in many human cancers, but the presence of these genes mutations determines the effectiveness of EGFR and HER2 tyrosine kinase inhibitors in the therapy of non-small cell lung cancer (NSCLC). Material and Methods: To search for insertions of the HER2 gene in exon 20 in 150 brain metastases of non-small cell lung cancer patients, we used a PCR technique based on analysis of amplified DNA fragment lengths. We also compared the HER2 mutational status with clinicopathologic features and the presence of EGFR and BRAF mutations. Results: HER2 mutation was present in one male, non-smoking patient with low differentiated adenocarcinoma (0.67% of all patients and 1.5% of patients with adenocarcinoma). The mutations of EGFR and BRAF genes were not found in HER2-mutated patient. Conclusions: The literature data suggests that patients with HER2 mutations may be sensitive to tyrosine kinase inhibitors of both EGFR and HER2 receptors (e.g., afatinib). Therefore, the identification of new driver mutations in NSCLC can improve the quality of patient care by enabling the use of correct molecularly targeted therapies. Full article

Introduction: Chronic obstructive pulmonary disease (COPD) is characterized by an airflow limitation that is usually progressive. The progression of COPD expressed as the rate of an annual decline in FEV₁ is very heterogeneous. Exercise capacity in COPD patients is often diminished and becomes worsened over the time. The purpose of the study was to examine how the change in FEV₁ and exercise capacity would deteriorate over long-term observation. Material and Methods: A total of 22 men with COPD were examined. At the beginning the average age was 59 ± 8.1 years and the mean post-bronchodilator FEV₁ was 52 ± 14.9% predicted. Pulmonary function testing was performed at entry and then each year for 10 years, and exercise testing on a cycle ergometer was performed at entry and after 10 years. Results: FEV₁ and maximum oxygen uptake (VO_2max), maximum mechanical work (W_max), maximum minute ventilation (V_Emax) and maximum tidal volume (V_Tmax) declined significantly over the observation time. The mean annual decline in FEV₁ was 42 ± 37 mL, and the mean decline for VO 2max was 30 ± 15 mL/min/yr and 0.44 ± 0.25 mL/min/kg/yr. Regression analysis revealed that the changes in FEV₁ do not predict changes in VO_2max. We observed a correlation between the annual change in V_Emax and annual change in VO_2max (r = 0.51; p < 0.05). The baseline FEV₁ (expressed as a percentage of predicted and in absolute values) is the predictor of FEV₁ annual decline (r = 0.74 and 0.82; p < 0.05). Conclusions: We observed over time deterioration in exercise capacity in COPD patients which is independent of decline in airflow limitation. The long term follow-up of exercise capacity is important in monitoring of COPD patients in addition to pulmonary function. Full article