RESUMO
SUMMARY: Birt-Hogg-Dubé (BHD) syndrome is a rare genetic pathology characterized by cutaneous fibrofolliculomas, pulmonary cysts and kidney tumours. Severe asthma is the most serious form of asthma that does not respond to standard treatments. We present the case of a 68 years-old male patient who had frequent respiratory tract infections, shortness of breath and decline in lung function, nasal polyposis and hypertrophy of the nasal turbinates, for this reason was treated as a severe asthmatic patient for several years with ICS + LABA and high doses of OCS. When we tried to reduce OCS the patient had worsening of the symptoms, we requested a HRTC scan that showed presence of several cysts spread ubiquitously. The patient had a family history of pneumothorax, for this reason we requested a genetic test that resulted in a heterozygous point mutation on exon 12 (c.1429 C > T) of FLCN gene. Despite the diagnosis of BHD syndrome, the patient's clinical condition kept on suggesting an underlying severe asthma and the blood tests we requested pointed out a high percentage of eosinophils, for this reason we opted for the administration of benralizumab that resulted in an excellent asthma control and increased quality of life.
Assuntos
Asma , Síndrome de Birt-Hogg-Dubé , Idoso , Anticorpos Monoclonais Humanizados , Asma/diagnóstico , Asma/tratamento farmacológico , Síndrome de Birt-Hogg-Dubé/complicações , Síndrome de Birt-Hogg-Dubé/diagnóstico , Síndrome de Birt-Hogg-Dubé/tratamento farmacológico , Humanos , Masculino , Proteínas Proto-Oncogênicas/genética , Qualidade de Vida , Proteínas Supressoras de Tumor/genéticaRESUMO
Exhaled breath temperature (EBT) is an expression of airway inflammation, an event that drives several lung diseases. The measurement of the exhaled breath temperature has recently been proposed as a popular tool in the diagnosis and monitoring of inflammatory lung diseases due to the fact that it is a non-invasive method. The influence of external factors on EBT, its reproducibility, and its sensitivity to treatment have already been explored. However, to reach clinical practice, EBT requires a complete validation that is still lacking. The aim of this study was to analyse the possible influence of an important internal variable, i.e the circadian rhythm on EBT values in a group of 24 healthy adult volunteers. We repeated measurement of EBT at different hours of the day: 8.00 AM, 12.00 AM, 4.00 PM, 8.00 PM and analysed the correlation with axillary temperature measurement at these times. The EBT resulted significantly different during daily measurements (8.00 AM vs 12.00 AM vs 4.00 PM vs 8.00 PM: 28.01±1.64°C vs 28.8±1.82°C vs 29.34±1.79°C vs 28.06±1.34°C). The highest EBT was reported at 4.00 PM and the lowest at 8.00 AM. For the first time we found an influence of the circadian rhythm on EBT. These data support the validation of the EBT necessary for its promotion in clinical practice.
Assuntos
Ritmo Circadiano/fisiologia , Expiração/fisiologia , Adulto , Feminino , Humanos , Masculino , Espirometria/instrumentação , TemperaturaRESUMO
Alpha-1-antitrypsin deficiency (AATD) is a genetic condition caused by SERPINA1 mutations, which culminates into lower protease inhibitor activity in the serum and predisposes to emphysema. Clinical manifestations of AATD are often associated to ZZ (p.Glu342Lys) and SZ (p.Glu264Val) genotypes and less frequently to rare deficiency or null alleles in heterozygous and homozygous states. We report a case of a 52-year-old woman with bronchiectasis without other potential causes other than an electrophoresis that showed a decrease of alpha-1 globin band and AAT levels below the normal value (78 mg/dl; v.n. 90-200 mg/dl). No S or Z mutation was identified, but sequencing analysis found a novel missense variant Ile74Asn (c.221T > A) in heterozygous state on an M3 allele (Glu400Asp) in the exon 2 of the SERPINA-1gene, probably leading to a dysfunctional protein. This mutation has never been previously identified, and it is interesting to note the association with bronchiectasis in the absence of emphysema.
Assuntos
Bronquiectasia/genética , Pulmão/diagnóstico por imagem , Mutação de Sentido Incorreto , Deficiência de alfa 1-Antitripsina/genética , alfa 1-Antitripsina/genética , Bronquiectasia/sangue , Bronquiectasia/diagnóstico por imagem , Bronquiectasia/fisiopatologia , Monóxido de Carbono , Feminino , Volume Expiratório Forçado , Genótipo , Heterozigoto , Humanos , Pulmão/fisiopatologia , Pessoa de Meia-Idade , Capacidade de Difusão Pulmonar , Volume Residual , Análise de Sequência de DNA , Tomografia Computadorizada por Raios X , Capacidade Pulmonar Total , Capacidade Vital , alfa 1-Antitripsina/sangue , Deficiência de alfa 1-Antitripsina/sangue , Deficiência de alfa 1-Antitripsina/diagnóstico , Deficiência de alfa 1-Antitripsina/fisiopatologiaRESUMO
BACKGROUND: Mitochondria contain their own DNA (MtDNA) that is very sensitive to oxidative stress and as a consequence could be damaged in quantity. Oxidative stress is largely recognized to play a key role in the pathogenesis of asthma and COPD and might have a role in the new intermediate phenotype ACOS (asthma-COPD overlap syndrome). The aim of this study was to investigate MtDNA alterations, as an expression of mitochondrial dysfunction, in ACOS and to verify whether they might help in the identification of this new phenotype and in its differentiation from asthma and COPD. METHODS: Ten (10) ACOS according to Spanish guidelines, 13 ACOS according to GINA guidelines, 13 COPD, 14 asthmatic patients and ten normal subjects were enrolled. They further underwent a blood, induced sputum and exhaled nitric oxide collection. Content of MtDNA and nuclear DNA (nDNA) were measured in the blood cells of patients by Real Time PCR. RESULTS: ACOS patients showed an increase of MtDNA/nDNA ratio. Dividing ACOS according to guidelines, those from the Spanish showed a higher value of MtDNA/nDNA compared to those from GINA/GOLD (92.69 ± 7.31 vs 80.68 ± 4.16). Spanish ACOS presented MtDNA/nDNA ratio closer to COPD than asthma. MtDNA was higher in asthmatic, COPD, GINA and Spanish ACOS patients compared to healthy subjects (73.30 ± 4.47-137.0 ± 19.45-80.68 ± 4.16-92.69 ± 7.31 vs 65.97 ± 20.56). CONCLUSION: We found an increase of MtDNA/nDNA ratio in ACOS subjects that led us to conclude that there is presence of mitochondrial dysfunction in this disease, that makes it closer to COPD than to asthma. Although the MtDNA/nDNA ratio results are a useful marker for differential diagnosis from asthma, COPD and ACOS, further studies are needed to confirm the potentiality of MtDNA/nDNA ratio and to a better characterization of ACOS.
Assuntos
Asma/genética , DNA Mitocondrial/genética , DNA/genética , Estresse Oxidativo , Doença Pulmonar Obstrutiva Crônica/genética , Idoso , Asma/complicações , Asma/imunologia , Testes Respiratórios , Estudos de Casos e Controles , Eosinofilia/complicações , Eosinofilia/imunologia , Feminino , Humanos , Hipersensibilidade Imediata/complicações , Hipersensibilidade Imediata/imunologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/imunologia , Reação em Cadeia da Polimerase em Tempo Real , Escarro/citologia , SíndromeRESUMO
AIM: The aim of the study was to investigate the effect of selective ETRA Sitaxsentan on viability and differentiation into myofibroblasts of lung fibroblasts derived from SSc-ILD patients and the ability of this drug to modify the lung fibroblast synthesis of VEGF, type I collagen and fibronectin. METHODS: Primary human lung fibroblast cultures were obtained from BAL of SSc-ILD patients. Cell cultures were exposed for 48 h to crescent concentrations of Sitaxsentan (10 -6M to 10 -4M). In these experimental conditions we evaluated cell viability through crystal violet staining, the production and mRNA expression of VEGF, fibronectin and type I collagen respectively through ELISA and real-Time PCR. Further, we detected alpha-Smooth Muscle Actin (α-SMA) through immunocytochemical assay. RESULTS: The lowest concentration of sitaxsentan (10-6M) did not affect fibroblasts viability; conversely at higher concentrations, sitaxsentan induced a significant inhibition of cell viability. Synthesis and mRNA expression of VEGF, type 1 collagen and fibronectin were significantly reduced in treated lung fibroblasts compared to the untreated ones, in a dose-dependent manner. At higher concentrations, Sitaxsentan reduced the expression of α-SMA. CONCLUSION: The results of this study show that sitaxentan is able in vitro to reduce both cell viability than production of VEGF and extra-cellular matrix components in SSc lung fibroblasts, confirming the anti-fibrotic potential of ETRA in SSc. The decreased expression of α-SMA in treated cells indicate that sitaxsentan may inhibit the fibroblast differentiation toward a myo-fibroblast phenotype and further support the hypothesis that the selective ETRAs may be beneficial in patients with SSc-ILD as anti fibrotic agents.
Assuntos
Antagonistas dos Receptores de Endotelina , Endotelinas/antagonistas & inibidores , Fibroblastos/efeitos dos fármacos , Isoxazóis/farmacologia , Pulmão/citologia , Escleroderma Sistêmico/patologia , Tiofenos/farmacologia , Actinas/metabolismo , Adulto , Idoso , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Colágeno Tipo I/biossíntese , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Fibronectinas/biossíntese , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Liso/metabolismo , Miofibroblastos/citologia , Fator A de Crescimento do Endotélio Vascular/biossínteseRESUMO
BACKGROUND: A recent intriguing carcinogenetic hypothesis for lung cancer foresees its viral aetiology. The human papilloma virus (HPV) is the main virus actually recognised in the pathogenesis of lung cancer. The aim of this study was to investigate, for the first time to our knowledge, the presence of HPV in the exhaled breath condensate (EBC) of lung cancer patients. MATERIALS AND METHOD: We enrolled 89 patients affected by lung cancer and 68 controls. HPV infections were investigated in their EBC, paired bronchial brushing and neoplastic lung tissue through genotyping. RESULTS: We were able to detect HPV in the EBC, bronchial brushing and neoplastic lung tissue. We described the presence of an HPV infection in 16.4% of the subjects affected by non-small cell lung cancer, but in none of the controls. HPV 16 and 31 turned out to be the most widespread genotypes. The HPV positivity in airways as well as in the smoking habit was seen to independently increase the individual's susceptibility to developing lung cancer. CONCLUSION: When summing up, we demonstrated the possibility to identify an HPV infection in the EBC of lung cancer patients; further, we supported the notion that the EBC is a suitable tool to study airway colonisation. That being said, although further studies are needed to confirm our results, we retain the study of HPV in EBC to be very interesting in terms of future programmes involving lung-cancer screening.
Assuntos
Testes Respiratórios , Neoplasias Pulmonares/virologia , Papillomaviridae/isolamento & purificação , Idoso , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Inclusão em ParafinaRESUMO
BACKGROUND: Respiratory viruses may persist in the airways of asthmatics between episodes of clinical worsening. We hypothesized that patients with clinically stable, severe asthma exhibit increased and more prolonged viral presence in the airways as compared to mild asthmatics and healthy controls. METHODS: Thirty-five subjects (no cold symptoms >4 weeks) entered a 12-week prospective study using three groups: clinically stable mild asthma (GINA 2) (n = 12, age 34.1 ± 13.4 year), severe asthma (GINA 4) (n = 12, age 49.3 ± 14.8 year) and healthy controls (n = 11, age 37.9 ± 14.2 year). All subjects underwent spirometry and completed a written questionnaire on asthma symptoms at baseline. Nasal and throat swabs, induced sputum samples, exhaled breath condensate and gelatine-filtered expired air were analysed at 0, 6 and 12 weeks by a multiplex real-time PCR assay for 14 respiratory viruses using adequate positive and negative controls. RESULTS: Thirty-two of 525 patient assessments (6%) showed a virus-positive sample. Among the 14 respiratory viruses examined, HRV, adenovirus, respiratory syncytial virus, parainfluenza 3&4, human bocavirus, influenza B and coronavirus were detected. When combining all sampling methods, on average 18% of controls and 30% of mild and severe asthmatics were virus positive, which was not different between the groups (P = 0.34). The longitudinal data showed a changing rather than persistent viral presence over time. CONCLUSION: Patients with clinically stable asthma and healthy controls have similar detection rates of respiratory viruses in samples from nasopharynx, sputum and exhaled air. This indicates that viral presence in the airways of stable (severe) asthmatics varies over time rather than being persistent.
Assuntos
Asma/virologia , Sistema Respiratório/virologia , Vírus/isolamento & purificação , Adulto , Estudos de Casos e Controles , Expiração , Seguimentos , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Nasofaringe/virologia , Estudos Prospectivos , Recidiva , Escarro/virologia , Adulto JovemRESUMO
BACKGROUND: Obstructive sleep apnea syndrome (OSAS) has been shown to be associated to upper and lower airways inflammation. Continuous positive airway pressure (CPAP) is the elective treatment of OSAS. The aim of the present study was to assess the effect of CPAP-therapy on airway and nasal inflammation. METHODS: In 13 non-smoking subjects affected by untreated OSAS and in 11 non-smoking normal volunteers, airway inflammation was detected by analyses of the induced sputum. In the OSAS group measurements were repeated after 1, 10 and 60 days of the appropriate CPAP treatment. In addition, in 12 subjects of the OSAS group, nasal inflammation was detected by the analysis of induced nasal secretions at baseline, and after 1, 10 and 60 days of CPAP treatment. RESULTS: OSAS patients, compared to normal controls, showed at baseline a higher percentage of neutrophils and a lower percentage of macrophages in the induced sputum. One, 10 and 60 days of appropriate CPAP-therapy did not change the cellular profile of the induced sputum. In addition, in the OSAS patients, the high neutrophilic nasal inflammation present under baseline conditions was not significantly modified by CPAP-therapy. Finally, no patients developed airway hyper-responsiveness after CPAP therapy. CONCLUSIONS: In OSAS subjects, the appropriate CPAP-therapy, while correcting the oxygen desaturation, does not modify the bronchial and nasal inflammatory profile.
Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Apneia Obstrutiva do Sono/terapia , Idoso , Testes de Provocação Brônquica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oximetria , Polissonografia , Testes de Função Respiratória , Apneia Obstrutiva do Sono/metabolismo , Apneia Obstrutiva do Sono/patologia , Apneia Obstrutiva do Sono/fisiopatologia , Escarro/metabolismoRESUMO
OBJECTIVE: The aim of the present study was to systematically assess the value of contrast-enhanced ultrasound (CEUS) vs. conventional transthoracic ultrasound (TUS) in improving diagnostic accuracy of percutaneous needle biopsy (PTNB) for subpleural lung lesions. PATIENTS AND METHODS: 232 patients with subpleural lesions were 1:1 randomly assigned to a group were CEUS was performed (n=116, mean age=65.5±5.6, M=69) or not (n=116, mean age=66.0±5.3, M=70). For CEUS study was used an injection of 4.8 mL of SonoVue (Bracco, Italy). For PTNB was employed a Menghini-modified technique with a semi-automatic 18-gauge needle. RESULTS: The mean diameter of subpleural lesions was 2.85±0.7 cm in the CEUS+ group and 2.95±0.6cm in the CEUS- group. Only 3 lesions, 1 in the CEUS+ group and 2 in the CEUS- group measured >5 cm. CEUS showed no superiority in terms of diagnostic accuracy compared to conventional TUS (p=0.34). Similar results were obtained in the sub-analysis of lesions sized between 1-2 cm (p=1.00) and 2-5 cm (p=0.08). As the lesion size increased, the detection rate of necrosis in lesions increased by CEUS (from 8% to 31%). CEUS showed no superiority in terms of diagnostic accuracy in the sub-analysis of necrotic lesions at CECT (p=0.38). AUC values for both the groups assessed an excellent diagnostic yield for TUS-PTNB (≥0.80). CONCLUSIONS: CEUS study does not improve the diagnostic accuracy of TUS-guided PTNB for peripheral lung lesions <5 cm of diameter. Further studies evaluating CEUS guidance for larger (>5 cm) and necrotic lesions are needed prior that its potential can be clarified.
Assuntos
Biópsia por Agulha/métodos , Aumento da Imagem/métodos , Pneumopatias/diagnóstico por imagem , Pneumopatias/patologia , Pulmão/diagnóstico por imagem , Pulmão/patologia , Ultrassonografia/métodos , Idoso , Meios de Contraste , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Female hormones play an important role in women's lung health, especially in asthma pathophysiology. Although a growing interest has recently been aroused in asthma related to short-term reproductive states, menopausal asthma has been little studied in the past. The aim of the present study was to explore airway inflammation in menopausal asthmatic women in a noninvasive manner. METHODS: Forty consecutive women with menopausal asthma, 35 consecutive women with premenopausal asthma and 30 age-matched healthy controls were enrolled in the study. Urinary LTE-4, induced sputum inflammatory cells, and exhaled LTE-4, IL-6, pH, and NO levels were measured in all the subjects enrolled. RESULTS: Women with menopausal asthma showed decreased estradiol concentrations, high sputum neutrophils, and exhaled IL-6. Women with premenopausal asthma presented instead an essentially eosinophilic inflammatory pattern. Higher urine and breath condensate LTE-4 concentrations were found in premenopausal and menopausal asthma compared to controls. CONCLUSION: Our results substantiate the existence of a new biological phenotype of menopausal asthma that is mainly characterized by neutrophilic airways inflammation and shares several characteristics of the severe asthma phenotype.
Assuntos
Asma , Menopausa , Asma/patologia , Asma/fisiopatologia , Estudos de Casos e Controles , Eosinófilos , Expiração , Feminino , Humanos , Concentração de Íons de Hidrogênio , Inflamação/patologia , Interleucina-4/análise , Leucotrieno E4/análise , Leucotrieno E4/urina , Pessoa de Meia-Idade , Neutrófilos/patologia , Óxido Nítrico/análise , Fenótipo , Pré-Menopausa , EscarroRESUMO
BACKGROUND: An altered balance of oxidants/antioxidants is one of the pathological mechanisms of many age-dependent disorders. We aimed to investigate the age-related airways oxidative stress, using non invasive, safe and repeatable techniques; to evaluate the correspondence between systemic and local oxidative stress in healthy subjects of different age ranges; to analyse the correlation between systemic and local oxidative stress with lung function and with cognitive impairment. METHODS: Thirty consecutive healthy high school graduated subjects (8 M, 22 F), divided in three ranges of age (< 35; between 35 and 60; > 60 years) were enrolled. All subjects underwent oxygen free radicals and exhaled nitric oxide measurement (by the diacron reactive oxygen metabolites test and by a rapid-response chemiluminescence nitric oxide analyzer), lung function tests, and cognitive impairment scales (Mini Mental State Examination and Geriatric Depression Scale). RESULTS: A significant increase of oxygen free radicals, exhaled nitric oxide, and Geriatric Depression Scale score and a significant decrease of forced expiratory volume in 1 second and forced expiratory vital capacity from younger to older subjects were identified. Moreover, the significant positive correlation between oxygen free radicals and exhaled nitric oxide, and between oxygen free radicals and exhaled nitric oxide with Geriatric Depression Scale score were found. The significant negative correlation between forced expiratory volume in 1 second and oxygen free radicals or exhaled nitric oxide was also demonstrated. CONCLUSIONS: Our data supports the role of progressive local oxidative stress in damaging the lung function and in inducing depression symptoms.
Assuntos
Envelhecimento/fisiologia , Envelhecimento/psicologia , Óxido Nítrico/análise , Estresse Oxidativo , Adulto , Idoso , Envelhecimento/sangue , Testes Respiratórios , Escalas de Graduação Psiquiátrica Breve , Transtornos Cognitivos/complicações , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/metabolismo , Depressão/complicações , Depressão/epidemiologia , Depressão/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espécies Reativas de Oxigênio/sangue , Testes de Função Respiratória , Adulto JovemRESUMO
BACKGROUND: Obstructive sleep apnoea (OSA) is associated with airways inflammation; a key role in this regard seems to be played by nitric oxide (NO). The aim of this study was to measure exhaled NO and expression of its enzyme, the inducible nitric oxide synthase (iNOS) in cells of induced sputum in OSA patients and in obese subjects without sleep apnoea and to correlate these inflammatory markers with severity of OSA. METHODS: We enrolled 18 obese patients with OSA (10 men, age 48.2 +/- 8.4 years), 15 obese patients without OSA (eight men, age 52.8 +/- 11 years) and 10 healthy subjects (five men, age 42 +/- 4 years). Exhaled NO was measured using a chemiluminescence analyser; iNOS expression was measured in the sputum cells by immunocytochemistry. RESULTS: Exhaled NO resulted significantly increased in OSA and in obese patients (23.1 +/- 2.1 and 17.9 +/- 2.1 p.p.b.) than in healthy subjects (7.2 +/- 0.6 p.p.b.; P < 0.001). OSA and obese patients showed a higher percentage of neutrophils and a lower percentage of macrophages in the induced sputum compared to healthy subjects. In addition, OSA and obese patients showed higher iNOS expression in neutrophils and in macrophages with respect to healthy subjects. A positive correlation between exhaled NO, iNOS expression and AHI was observed. CONCLUSIONS: These data confirm the presence of airway inflammation in OSA and in obese patients, and suggest the possible role for NO and iNOS expression in neutrophils of the induced sputum as noninvasive markers to identify and monitor the airway inflammation in these subjects.
Assuntos
Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico/metabolismo , Obesidade/metabolismo , Apneia Obstrutiva do Sono/metabolismo , Escarro/metabolismo , Adulto , Testes Respiratórios , Feminino , Fluxo Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Polissonografia , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono/classificação , Apneia Obstrutiva do Sono/complicaçõesRESUMO
Chronic obstructive pulmonary diseases (COPD) is a pulmonary disease characterized by systemic abnormalities. The aim of this study is to investigate inflammation and systemic effects in mild COPD. Twenty-seven mild stable smoking related COPD patients and 15 age-matched healthy subjects were enrolled in the study. IL-6, TNF-alpha and IL-4 in plasma, sputum and exhaled breath condensate were measured. We also measured exhaled nitric oxide (NO) and pH in sputum and in breath condensate. Moreover, fat-free mass, body mass index (BMI), respiratory muscle strength, plasma oxidative stress and C-reactive protein (CRP) were measured. Higher concentrations were found of CRP, of diacron reactive oxygen metabolites (DROMs) and of IL-6, TNF-alpha and IL-4 either in plasma or in supernatant of induced sputum or in exhaled breath condensate of COPD subjects compared to healthy controls. Furthermore, higher concentrations were observed of exhaled NO and lower exhaled pH in breath condensate of COPD when compared with healthy subjects. In the group of COPD patients, the subjects with airway reversibility showed an increase of sputum eosinophils and exhaled NO, whereas the subjects without airway obstruction reversibility showed an increase in sputum neutrophils, TNF-alpha and IL-6. We also found a trend towards a decrease in fat-free mass and respiratory muscle strength in COPD compared to healthy subjects and a negative correlation between these systemic indices (fat-free mass, maximal inspiratory pressure, maximal expiratory pressure) and TNF-alpha concentrations in the blood, sputum and breath condensate. We conclude that mild COPD subjects present an increase in inflammatory markers in blood and in airways of similar pattern and furthermore, the neutrophilic pattern of airway inflammation observed in the group of COPD subjects without an airway obstruction reversibility makes it more likely that systemic features are present.
Assuntos
Inflamação/patologia , Estresse Oxidativo/fisiologia , Doença Pulmonar Obstrutiva Crônica/patologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Adulto , Composição Corporal , Índice de Massa Corporal , Testes Respiratórios , Proteína C-Reativa/metabolismo , Contagem de Células , Feminino , Humanos , Concentração de Íons de Hidrogênio , Interleucina-4/biossíntese , Interleucina-6/biossíntese , Masculino , Força Muscular/fisiologia , Óxido Nítrico/metabolismo , Testes de Função Respiratória , Músculos Respiratórios/fisiopatologia , Sistema Respiratório/patologia , Sistema Respiratório/fisiopatologia , Escarro/citologia , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Brittle asthma is a clinical phenotype of the disease at the severe end of the spectrum. Type 1 brittle asthma is characterised by a maintained wide PEF variability (> 40% diurnal variation for > 50% of the time over a period of at least 150 days) despite considerable medical therapy including a dose of inhaled steroids of at least 1500 pg of beclomethasone or equivalent. Type 2 brittle asthma is characterised by sudden acute attacks occurring in less than three hours without an obvious trigger on a background of apparent normal airway function or well controlled asthma. Mechanisms behind the development of brittle asthma include smooth muscle contraction and edema of the airways, which are supported by chronic airway inflammation. Allergy reactions, impairment of local immunity, respiratory infections, psycho-social disorders and reduced perception of worsening airway function are the risk factors for brittle asthma. The diagnosis is based on the analysis of specific symptoms, role of triggers, personal or family history, measurement of lung function and PEF monitoring. Pharmacological treatment of type 1 brittle asthma in addition to the high doses of inhaled and/or oral steroids and bronchodilators includes subcutaneous injections of beta2 agonist and inhalation of long acting beta2 agonist. The treatment of patients with type 2 brittle asthma includes exclusion of allergen exposure, identification of triggers, self management and management of acute attacks.
Assuntos
Asma , Asma/diagnóstico , Asma/etiologia , Asma/terapia , Humanos , Pico do Fluxo ExpiratórioAssuntos
Cromossomos Humanos Par 19/genética , Cromossomos Humanos Par 3/genética , Repetições de Microssatélites/genética , Mutação , Abandono do Hábito de Fumar , Fumar/genética , Fumar/terapia , Adulto , Idoso , Testes Respiratórios/métodos , Monóxido de Carbono/análise , DNA/genética , Expiração , Feminino , Loci Gênicos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The mechanism responsible for the reversibility of airflow limitation in stable chronic obstructive pulmonary disease (COPD) patients is unknown. The aim of this study is to assess the relationship between the reversibility of airflow limitation, the redox balance and the inflammatory cells in the sputum of patients with stable COPD. For this purpose we examined 15 normal healthy control subjects and 20 nonatopic COPD patients. The COPD patients were divided into two groups: reversible COPD (increase in FEV1> 200 ml and/or > or =12> or = after 200 microg of inhaled salbutamol) or non-reversible COPD. GSH, GSSG were measured in induced sputum and blood. Protein carbonyls were evaluated by WB in sputum and IL-4 and IL-6 and TNF-alpha in plasma and sputum. GSH oxidation and protein oxidation were lower in reversible COPD patients than in those with no reversibility. The sputum eosinophil count was significantly higher in the reversible group than in the non-reversible group, and IL-4 concentration was higher in the same patients both in sputum and in plasma. In contrast, IL-6 and TNF-alpha were increased in non-reversible COPD patients in both biological samples. We conclude that airflow reversibility in COPD patients is associated with airway oxidative stress and activation of eosinophil inflammatory pattern in sputum and blood, suggesting that these patients could respond to specific pharmacological treatment.
Assuntos
Estresse Oxidativo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Escarro/metabolismo , Adulto , Citocinas/biossíntese , Feminino , Volume Expiratório Forçado , Glutationa/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Óxido Nítrico/fisiologia , Doença Pulmonar Obstrutiva Crônica/patologia , Escarro/citologia , Superóxidos/metabolismoRESUMO
The constant increase in allergic diseases in western countries is correlated with changes in lifestyle and with the deterioration of the air inhaled by the inhabitants because of the growing concentrations of pollutant substances present. Within a population at risk, i.e., the inhabitants of cities, a group of subjects at even higher risk was selected, whose job exposes them to automobile exhaust fumes for many hours a day. All the study subjects underwent allergological screening and spirometry. The results obtained show an overall increase of respiratory allergic diseases but no increased sensitisation to latex. It therefore seems plausible that, besides social and lifestyle changes, the deterioration of the quality of the air could be considered responsible, at least in part, for the growing numbers of allergic subjects. This study offers an opportunity to reconsider the validity of the hygiene hypothesis as an explanation for the increase of allergic disease in western countries, although recent reports have indicated that a sedentary lifestyle may also contribute, together with environmental degradation, to the notably increased prevalence of allergic diseases in large cities in industrialized nations.
Assuntos
Hipersensibilidade ao Látex/epidemiologia , Adulto , Alérgenos , Coleta de Dados , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Vigilância da População , EspirometriaRESUMO
Idiopathic pulmonary fibrosis is a chronic progressive disease of lung interstitium of unknown etiology with poor prognosis. In patients with IPF, the incidence of lung cancer is much higher than that in the general population. The identification of noninvasive biomarkers for early diagnosis of IPF is of great relevance in consideration of the management of these patients. Among the noninvasive omic markers, an increasing interest has been directed toward the study of genetic alterations of microsatellites (MAs) in exhaled breath condensate (EBC). The aim of this preliminary study was to investigate the MAs, located in chromosomal regions 8p21.3-q11.1 and 17q11.2-q21, that harbor tumor suppressor genes, in EBC and in the paired whole blood (WB) of IPF patients. Eleven IPF patients were compared with 10 healthy control subjects. All subjects underwent collection of the EBC and WB. The EBC was collected using a condenser. Four microsatellite markers (THRA1, D17S579, D17S250 and D8S137) were used for the analysis of MAs. The EBC-DNA and WB-DNA were amplified by PCR; PCR products were analyzed using the ABI Prism 310 DNA. Microsatellite alterations were found in 58.82 % of EBC-DNA and 12.50 % of WB-DNA in patients with IPF (p < 0.01). None of the healthy subjects exhibited MAs in the studied markers. Our findings suggest that these genetic alterations, studied in EBC, may play an important role in the complex genetic basis of IPF. Since these MAs are frequently detected in cancer, they might explain the higher relative risk of tumorigenesis in this disease.
Assuntos
Fibrose Pulmonar Idiopática/genética , Neoplasias Pulmonares/genética , Repetições de Microssatélites , Idoso , Sangue , Testes Respiratórios , Estudos de Casos e Controles , Cromossomos Humanos Par 17 , Cromossomos Humanos Par 8 , Expiração , Feminino , Marcadores Genéticos , Humanos , Perda de Heterozigosidade , MasculinoRESUMO
Mitochondrial DNA (MtDNA) has been studied as an expression of oxidative stress in asthma, COPD, lung cancer and obstructive sleep apnea, but it has been mainly investigated systemically, although the pathogenetic mechanisms begin in the airways and only later progress to systemic circulation. The aim of this study was to investigate the MtDNA alterations in the exhaled breath condensate (EBC) of patients with asthma, COPD and asthma-COPD overlap syndrome (ACOS). In order to analyze better what happens to mitochondria, both locally and systemically, we compared MtDNA/nDNA in blood and EBC of paired patients. Thirteen (13) COPD patients, 14 asthmatics, 23 ACOS (10 according to Spanish guidelines, 13 in line with GINA guidelines) and 12 healthy subjects were enrolled. Patients underwent clinical and functional diagnostic tests as foreseen by the guidelines. They underwent blood and EBC collection. Content of MtDNA and nuclear DNA (nDNA) was measured in the blood cells and EBC of patients by Real Time PCR. The ratio between MtDNA/nDNA was calculated. For the first time we were able to detect MtDNA/nDNA in the EBC. We found higher exhaled MtDNA/nDNA in COPD, asthmatic and ACOS patients respectively compared to healthy subjects (21.9 ± 4.9 versus 6.51 ± 0.21, p < 0.05; 7.9 ± 2.5 versus 6.51 ± 0.21, p = 0.06; 18.3 ± 3.4 versus 6.51 ± 0.21, p < 0.05). The level of exhaled MtDNA/nDNA was positively correlated with the plasmatic one. The levels of MtDNA/nDNA in the EBC, as expression of oxidative stress, are increased in COPD, asthmatic and ACOS patients compared to healthy subjects. These are preliminary results in a small number of well characterized patients that requires confirmation on a larger population. We support new studies directed toward the analysis of exhaled MtDNA/nDNA as a new exhaled non-invasive marker in other inflammatory/oxidative airways diseases.
Assuntos
Asma/metabolismo , Testes Respiratórios/métodos , DNA Mitocondrial/análise , Estresse Oxidativo/fisiologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Idoso , Asma/genética , Biomarcadores/análise , Expiração , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/genéticaRESUMO
BACKGROUND: This retrospective study aimed at evaluating long-term effects of Omalizumab in elderly asthmatics in a real-life setting. METHODS: 105 consecutive severe asthmatics (GINA step 4-5; mean FEV1% predicted:66 ± 15.7) treated with Omalizumab for at least 1 year (treatment mean duration 35.1 ± 21.7 months) were divided into 3 groups according to their age at Omalizumab treatment onset: 18-39, 40-64 and ≥ 65 years. RESULTS: Comorbidities, number of overweight/obese subjects and patients with late-onset asthma were more frequent among older people. A similar reduction of inhaled corticosteroids dosage and SABA on-demand therapy was observed in all groups during Omalizumab treatment; a similar FEV1 increased was also observed. Asthma Control Test (ACT) improved significantly (p < 0.001) in the three groups, increasing from 15 [IQR:12-18] to 24 [IQR:22-25] in younger subjects, from 14 [IQR:10-16] to 21 [IQR:20-23] in the 40-64-year-group and from 15 [IQR:12-16] to 20 [IQR:18-22] in elderly patients where improvement was lower (p = 0.039) compared to younger people. Asthma exacerbations decreased significantly after Omalizumab but the percentage of exacerbation-free patients was higher in younger people (76.9%) compared to middle aged patients (49.2%) and the elderly (29%) (p = 0.049). After Omalizumab treatment, the risk for exacerbations was lower in subjects aged 40-64 (OR = 0.284 [CI95% = 0.098-0.826], p = 0.021) and 18-39 (OR = 0.133 [CI95% = 0.026-0.678], p = 0.015), compared to elderly asthmatics. Also, a significantly reduced ACT improvement (ß = -1.070; p = 0.046) passing from each age class was observed. CONCLUSION: Omalizumab improves all asthma outcomes independently of age, although the magnitude of the effects observed in the elderly seems to be lower than in the other age groups.