RESUMO
BACKGROUND: Ivacaftor is a significant innovation in the treatment of cystic fibrosis (CF) with gating mutations. A substantial percentage of patients with CF have severe lung involvement, but these patients are usually excluded from phase III clinical trials. Thus, the effectiveness of ivacaftor in this population has not been fully determined. METHODS: Data were collected from Italian CF centers with patients enrolled in an ivacaftor compassionate use programme (percent predicted [pp] forced expiratory volume in 1 second [FEV1 ] < 40%, or on lung transplant waiting list, or with a fast worsening trend of lung function). Data were collected for 1 year before and 1 year after ivacaftor commencement. RESULTS: Thirteen patients received ivacaftor for a median of 320 days. Mean (SD) ppFEV1 increased from 35.1% (14.3%) before treatment to 46.6% (18.8%) after 12 months of treatment (absolute increase 11.5%, relative increase 32.8%). Mean distance of the 6-minute walking test improved significantly, from 535.1 m before to 611.6 m after 12 months of treatment (P = .002). The number of pulmonary exacerbations decreased significantly, from 57 during the year before ivacaftor to 28 in the year following ivacaftor (P = .0048). Five of the 13 patients (38.5%) had no exacerbations during the 12 months after starting ivacaftor. Median weight increased significantly, from 52.7 kg to 55.6 kg (P = .0031). Mean (SD) sweat chloride concentration decreased significantly, from 99.5 (22.8) mmol/L to 39.3 (15.8) mmol/L (P < .0001). No safety concerns were registered. CONCLUSIONS: Ivacaftor was safe and effective in patients with CF with severe lung disease and non-G551D gating mutations.
Assuntos
Aminofenóis/uso terapêutico , Agonistas dos Canais de Cloreto/uso terapêutico , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/tratamento farmacológico , Quinolonas/uso terapêutico , Adolescente , Adulto , Criança , Cloretos/análise , Ensaios de Uso Compassivo , Fibrose Cística/genética , Feminino , Volume Expiratório Forçado , Humanos , Ativação do Canal Iônico/genética , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Mutação , Testes de Função Respiratória , Estudos Retrospectivos , Suor/químicaRESUMO
The Lung Clearance Index (LCI) is an index derived from washout recordings, able to detect early peripheral airway damage in subjects with cystic fibrosis (CF) with a greater sensitivity than spirometry.LCI is a marker of overall lung ventilation inhomogeneity; in fact, as pulmonary ventilation worsens, the number of tidal breaths and the expiratory volumes required to clear the lungs of a marker gas are increased, as documented by a greater value.In the field of CF, LCI allows indirect investigation of the small airways (< 2 mm) the site where, from a pathophysiologic point of view, the disease begins due to the defect of the CF transmembrane-conductance regulator (CFTR) protein. Infant pulmonary function changes seem to occur before clinically overt symptoms of lower respiratory illness occur.When performing the test, it is important to refer to the American Thoracic Society and European Respiratory Society consensus statements and apply a strict standardization.In Italy the first tests were carried out in 2014 for research purpose and now approximately 10 centers are collecting data and are experiencing a consistency in repeating exams.Currently in Italian centers children at pre-school age are the main target: in this population it is important to have a sensitive and feasible test, non-invasive, that can be performed at tidal volume without sedation, and requiring minimal cooperation and coordination, and that can be used longitudinally over time. Another target could be the transplanted subjects to detect early signs of lung function decline.The content of this paper captures the experience and discussions among some of the Italian centers where LCI is currently used for research and/or in clinical practice about the method and the need to have a common approach.The aim of this paper is not to describe the methodology of MBW, but to inform the pediatric community about the possible application of LCI in CF.
Assuntos
Fibrose Cística/diagnóstico , Criança , Pré-Escolar , Fibrose Cística/fisiopatologia , Volume Expiratório Forçado/fisiologia , Humanos , Itália , Volume de Ventilação Pulmonar/fisiologiaAssuntos
Fibrose Cística/cirurgia , Cirurgia Endoscópica por Orifício Natural , Qualidade de Vida , Rinite/cirurgia , Sinusite/cirurgia , Adulto , Doença Crônica , Fibrose Cística/psicologia , Feminino , Humanos , Masculino , Rinite/psicologia , Sinusite/psicologia , Inquéritos e Questionários , Resultado do TratamentoRESUMO
OBJECTIVE: The implementation of cystic fibrosis (CF) newborn screening (NBS) has led to identification of infants with a positive NBS test but inconclusive diagnosis classified as "CF screen positive, inconclusive diagnosis" (CFSPID). We retrospectively evaluated the prevalence and clinical outcome of CFSPID infants diagnosed by 2 NBS algorithms in the period from 2011 to 2016 in the Tuscany region of Italy. METHODS: In 2011-2016, we assessed the diagnostic impact of DNA analysis on the NBS 4-tier algorithm [immunoreactive trypsin (IRT) - meconium lactase - IRT2 - sweat chloride (SC)]. All CFSPID patients repeated SC testing every 6â¯months, and CFTR gene analysis was performed (detection rate 98%). We reclassified children as: CF diagnosis in presence of at least 2 pathological SC results; healthy carrier or healthy in presence of at least 2 normal SC results for age and either 1 or 0 CF-causing mutations, respectively. RESULTS: We identified 32 CF and 50 CFSPID cases: 20/50 (40%) were diagnosed only by the IRT-DNA-SC algorithm and 16/50 (32%) only by IRT-meconium lactase-IRT2-SC. Both protocols identified the remaining 14 cases (28%). Thirty-seven of 50 (74%) CFSPID patients had a conclusive diagnosis on December 31, 2017:5 (10%) CF, 17 (34%) healthy and 15 (30%) healthy carriers; 13/50 (26%) cases were asymptomatic with persistent intermediate SC and followed as CFSPID (CF:CFSPID ratio 2.85:1). CONCLUSIONS: In 6â¯years, the CF:CFSPID ratio modified from 0.64:1 to 2.85:1, and 10% of CFSPID cases progressed to CF. Genetic analysis improved positive predictive value and identified a higher number of CFSPID infants progressing to CF.
Assuntos
Fibrose Cística/diagnóstico , Triagem Neonatal , Algoritmos , Humanos , Recém-Nascido , Itália , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
BACKGROUND: Few studies, based on a limited number of patients using non-uniform therapeutic protocols, have analyzed Methicillin-resistant Staphylococcus aureus (MRSA) eradication. METHODS: In a randomized multicenter trial conducted on patients with new-onset MRSA infection we evaluated the efficacy of an early eradication treatment (arm A) compared with an observational group (B). Arm A received oral rifampicin and trimethoprim/sulfamethoxazole (21 days). Patients' microbiological status, FEV1, BMI, pulmonary exacerbations and use of antibiotics were assessed. RESULTS: Sixty-one patients were randomized. Twenty-nine (47.5%) patients were assigned to active arm A and 32 (52.5%) patients to observational arm B. Twenty-nine (47.5%) patients, 10 patients in arm A and 19 in arm B, dropped out of the study. At 6 months MRSA was eradicated in 12 (63.2%) out of 19 patients in arm A while spontaneous clearance was observed in 5 (38.5%) out of 13 patients in arm B. A per-protocol analysis showed a 24.7% difference in the proportion of MRSA clearance between the two groups (z = 1.37, P(Z>z) = 0.08). Twenty-seven patients, 15 (78.9%) out of 19 in arm A and 12 (92.3%) out of 13 in arm B, were able to perform spirometry. The mean (±SD) FEV1 change from baseline was 7.13% (±14.92) in arm A and -1.16% (±5.25) in arm B (p = 0.08). In the same period the BMI change (mean ±SD) from baseline was 0.54 (±1.33) kg/m2 in arm A and -0.38 (±1.56) kg/m2 in arm B (p = 0.08). At 6 months no statistically significant differences regarding the number of pulmonary exacerbations, days spent in hospital and use of antibiotics were observed between the two arms. CONCLUSIONS: Although the statistical power of the study is limited, we found a 24.7% higher clearance of MRSA in the active arm than in the observational arm at 6 months. Patients in the active arm A also had favorable FEV1 and BMI tendencies.
Assuntos
Antibacterianos/administração & dosagem , Fibrose Cística/tratamento farmacológico , Staphylococcus aureus Resistente à Meticilina , Rifampina/administração & dosagem , Infecções Estafilocócicas/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Adolescente , Adulto , Criança , Pré-Escolar , Fibrose Cística/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Estafilocócicas/fisiopatologia , Fatores de TempoRESUMO
Pharmacological rescue of mutant cystic fibrosis transmembrane conductance regulator (CFTR) in cystic fibrosis (CF) depends on the specific defect caused by different mutation classes. We asked whether a patient with the rare p.Gly970Asp (c.2909G>A) mutation could benefit from CFTR pharmacotherapy since a similar missense mutant p.Gly970Arg (c.2908G>C) was previously found to be sensitive to potentiators in vitro but not in vivo. By complementary DNA transfection, we found that both mutations are associated with defective CFTR function amenable to pharmacological treatment. However, analysis of messenger RNA (mRNA) from patient's cells revealed that c.2908G>C impairs RNA splicing whereas c.2909G>A does not perturb splicing and leads to the expected p.Gly970Asp mutation. In agreement with these results, nasal epithelial cells from the p.Gly970Asp patient showed significant improvement of CFTR function upon pharmacological treatment. Our results underline the importance of controlling the effect of CF mutation at the mRNA level to determine if the pharmacotherapy of CFTR basic defect is appropriate.
Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Fibrose Cística/genética , Mutação Puntual , Códon , Fibrose Cística/metabolismo , Células HEK293 , Humanos , Fenótipo , Splicing de RNA , TransfecçãoRESUMO
BACKGROUND: A clinical heterogeneity was reported in patients with Cystic Fibrosis (CF) with the same CFTR genotype and between siblings with CF. METHODS: We investigated all clinical aspects in a cohort of 101 pairs of siblings with CF (including 6 triplets) followed since diagnosis. RESULTS: Severe lung disease had a 22.2% concordance in sib-pairs, occurred early and the FEV1% at 12 years was predictive of the severity of lung disease in the adulthood. Similarly, CF liver disease occurred early (median: 15 years) and showed a concordance of 27.8% in sib-pairs suggesting a scarce contribution of genetic factors; in fact, only 2/15 patients with liver disease in discordant sib-pairs had a deficiency of alpha-1-antitrypsin (a known modifier gene of CF liver phenotype). CF related diabetes was found in 22 pairs (in 6 in both the siblings). It occurred later (median: 32.5 years) and is strongly associated with liver disease. Colonization by P. aeruginosa and nasal polyposis that required surgery had a concordance > 50% in sib-pairs and were poorly correlated to other clinical parameters. The pancreatic status was highly concordant in pairs of siblings (i.e., 95.1%) but a different pancreatic status was observed in patients with the same CFTR mutations. This suggests a close relationship of the pancreatic status with the "whole" CFTR genotype, including mutations in regulatory regions that may modulate the levels of CFTR expression. Finally, a severe course of CF was evident in a number of patients with pancreatic sufficiency. CONCLUSIONS: Physicians involved in care of patients with CF and in genetic counseling must be aware of the clinical heterogeneity of CF even in sib-pairs that, at the state of the art, is difficult to explain.
Assuntos
Portador Sadio/microbiologia , Fibrose Cística/fisiopatologia , Diabetes Mellitus/etiologia , Insuficiência Pancreática Exócrina/etiologia , Hepatopatias/etiologia , Íleo Meconial/etiologia , Irmãos , Adolescente , Adulto , Criança , Fibrose Cística/complicações , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Feminino , Volume Expiratório Forçado , Genótipo , Humanos , Lactente , Recém-Nascido , Itália , Masculino , Pessoa de Meia-Idade , Mutação , Pólipos Nasais/complicações , Pólipos Nasais/cirurgia , Orofaringe/microbiologia , Fenótipo , Pseudomonas aeruginosa , Índice de Gravidade de Doença , Escarro/microbiologia , Adulto Jovem , alfa 1-Antitripsina/genéticaRESUMO
BACKGROUND: Recurrent (RP) and chronic pancreatitis (CP) may complicate Cystic Fibrosis (CF). It is still unknown if mutations in genes involved in the intrapancreatic activation of trypsin (IPAT) or in the pancreatic secretion pathway (PSP) may enhance the risk for RP/CP in patients with CF. METHODS: We enrolled: 48 patients affected by CF complicated by RP/CP and, as controls 35 patients with CF without pancreatitis and 80 unrelated healthy subjects. We tested a panel of 8 genes involved in the IPAT, i.e. PRSS1, PRSS2, SPINK1, CTRC, CASR, CFTR, CTSB and KRT8 and 23 additional genes implicated in the PSP. RESULTS: We found 14/48 patients (29.2%) with mutations in genes involved in IPAT in the group of CF patients with RP/CP, while mutations in such genes were found in 2/35 (5.7%) patients with CF without pancreatitis and in 3/80 (3.8%) healthy subjects (p < 0.001). Thus, we found mutations in 12 genes of the PSP in 11/48 (22.9%) patients with CF and RP/CP. Overall, 19/48 (39.6%) patients with CF and RP/CP showed one or more mutations in the genes involved in the IPAT and in the PSP while such figure was 4/35 (11.4%) for patients with CF without pancreatitis and 11/80 (13.7%) for healthy controls (p < 0.001). CONCLUSIONS: The trans-heterozygous association between CFTR mutations in genes involved in the pathways of pancreatic enzyme activation and the pancreatic secretion may be risk factors for the development of recurrent or chronic pancreatitis in patients with CF.
Assuntos
Fibrose Cística/genética , Pancreatite Crônica/genética , Adolescente , Adulto , Criança , Pré-Escolar , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Predisposição Genética para Doença , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Mutação , Pâncreas/metabolismo , Recidiva , Risco , Tripsina/metabolismo , Adulto JovemRESUMO
BACKGROUND: Cystic Fibrosis (CF) Centers are involved in the decisions regarding the eligibility of CF patients with end-stage lung disease and timing for inclusion on waiting lists (WL) for lung transplantation (LT). There are currently no data on the mortality rates of Italian CF patients on WL and during the first year after LT and we aimed to assess these outcomes by surveying the CF Centers. METHODS: A survey was sent to Italian CF Centers which were requested to report the age at which all CF subjects included on the WL between 2010 and 2014 were included on the list, admitted to either standard or urgent LT, or had died either while on the WL or within the first 3 and 12 months after LT. All outcomes were recorded by December 31, 2015. RESULTS: Two hundred fifty-nine CF subjects were included on the WL during the 5-year study period. The mortality rate during the WL was 19.3% and was not associated with sex, age at inclusion on the WL or standard or urgent access to LT. 159 (61.4%) subjects underwent LT, 46 (28.9%) with urgent procedure. Deaths within the first 3 and 12 months after LT were significantly more prevalent in individuals who underwent urgent LT compared to those with standard LT (p < 0.01). CONCLUSIONS: The mortality of Italian CF patients, included in our survey, was about twice that reported by the National Transplant Center for all LT indications, including CF, during the same time period and despite the introduction of urgent LT. The latter was associated with an unfavorable early outcome compared to standard LT.
Assuntos
Fibrose Cística/cirurgia , Transplante de Pulmão , Sistema de Registros , Listas de Espera/mortalidade , Adulto , Estudos Transversais , Fibrose Cística/epidemiologia , Feminino , Humanos , Incidência , Itália/epidemiologia , Masculino , Inquéritos e Questionários , Taxa de Sobrevida/tendências , Adulto JovemRESUMO
BACKGROUND: An increasing number of patients have been described as having a number of Cystic Fibrosis Transmembrane conductance Regulator (CFTR) variants for which it lacks a clear genotype-phenotype correlation. We assesses the clinical features of patients bearing the S737F (p.Ser737Phe) CFTR missense variant and evaluated the residual function of CFTR protein on nasal epithelial cells (NEC). METHODS: A retrospective database was performed from individuals homozygous or compound heterozygous for the S737F variant followed in the Cystic Fibrosis (CF) Centre of Florence. We performed a nasal brushing in cooperating patients and compared the results with those of patients followed in the pediatric CF Centre of Naples. RESULTS: 9/295 (3%) subjects carrying at least S737F CFTR variant on one allele were identified. Patients were diagnosed in 7/9 cases by newborn screening and in two cases for dehydration with hypochloremic metabolic alkalosis; at diagnosis sweat chloride levels (SCL) were in the pathological range in only one case. After a mean follow up of 8,6 years (range 0,5-15,8), SCL were in the pathological range in 8/9 cases (mean age at CF diagnosis: 1,5 years), all patients were pancreatic sufficiency and respiratory function was normal. The gating activity on NEC was 15.6% and 12.7% in two patients compound heterozygous for W1282X and DelE22_24, while it was ranged between 6,2% and 9,8% in CF patients. CONCLUSIONS: S737F is a CFTR mutation associated to hypochloremic alkalosis in childhood, mild CF phenotype in teenage years and a residual function of CFTR protein.
Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/epidemiologia , Fibrose Cística/genética , Predisposição Genética para Doença/epidemiologia , Mutação/genética , Adolescente , Distribuição por Idade , Criança , Pré-Escolar , Fibrose Cística/fisiopatologia , Bases de Dados Factuais , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Itália/epidemiologia , Masculino , Triagem Neonatal , Estudos Retrospectivos , Medição de Risco , Distribuição por SexoRESUMO
BACKGROUND: Cystic fibrosis, like other chronic diseases, is a risk factor for the development of elevated symptoms of depression and anxiety. The objective of this study was to investigate the prevalence of anxiety and depression in Italian patients with CF and their parents. METHODS: The Hospital Anxiety and Depression Scale (HADS) and Center for Epidemiologic Studies Depression Scale (CES-D) questionnaires were administered to a sample of patients and their parents recruited at the cystic fibrosis centers in Italy. RESULTS: Elevated levels of anxiety were higher in mothers than in fathers, and also higher in female patients than in male patients. A correlation between elevated levels of anxiety/depression and geographical area also emerged. Patient anxiety (OR 2.33) and depression (OR 4.09) were significantly associated with forced expiratory volume in one second (FEV1) <40% and forced vital capacity (FVC) <80% (OR 1.60 and 1.61, respectively). CONCLUSIONS: Cystic fibrosis increases the risk of developing anxiety and depression in female patients and in mothers. Geographical differences were observed, with higher anxiety and depression in southern Italy for parents, but not for patients. Anxiety and depression levels also depend on clinical status. Pediatr Pulmonol. 2016;51:1311-1319. © 2016 Wiley Periodicals, Inc.
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Transtornos de Ansiedade/epidemiologia , Ansiedade/epidemiologia , Cuidadores/estatística & dados numéricos , Fibrose Cística/epidemiologia , Depressão/epidemiologia , Transtorno Depressivo/epidemiologia , Pai/estatística & dados numéricos , Mães/estatística & dados numéricos , Adolescente , Ansiedade/psicologia , Transtornos de Ansiedade/psicologia , Cuidadores/psicologia , Criança , Doença Crônica , Fibrose Cística/fisiopatologia , Fibrose Cística/psicologia , Depressão/psicologia , Transtorno Depressivo/psicologia , Pai/psicologia , Feminino , Volume Expiratório Forçado , Humanos , Itália/epidemiologia , Masculino , Mães/psicologia , Pais/psicologia , Prevalência , Fatores de Risco , Índice de Gravidade de Doença , Inquéritos e Questionários , Capacidade Vital , Adulto JovemRESUMO
UNLABELLED: The European Cystic Fibrosis Society Clinical Trial Network (ECFS-CTN) has established a Standardization Committee to undertake a rigorous evaluation of promising outcome measures with regard to use in multicentre clinical trials in cystic fibrosis (CF). The aim of this article is to present a review of literature on clinimetric properties of the infant raised-volume rapid thoracic compression (RVRTC) technique in the context of CF, to summarise the consensus amongst the group on feasibility and answer key questions regarding the promotion of this technique to surrogate endpoint status. METHODS: A literature search (from 1985 onwards) identified 20 papers that met inclusion criteria of RVRTC use in infants with CF. Data were extracted and tabulated regarding repeatability, validity, correlation with other outcome measures, responsiveness and reference values. A working group discussed the tables and answered 4 key questions. RESULTS: Overall, RVRTC in particular forced expiratory volume in 0.5s, showed good clinimetric properties despite presence of individual variability. Few studies showed a relationship between RVRTC and inflammation and infection, and to date, data remains limited regarding the responsiveness of RVRTC after an intervention. Concerns were raised regarding feasibility in multi-centre studies and availability of reference values. CONCLUSION: The ECFS-CTN Working Group considers that RVRTC cannot be used as a primary outcome in clinical trials in infants with CF before universal standardization of this measurement is achieved and implementation of inter-institutional networking is in place. We advise its use currently in phase I/II trials and as a secondary endpoint in phase III studies. We emphasise the need for (1) more short-term variability and longitudinal 'natural history' studies, and (2) robust reference values for commercially available devices.
Assuntos
Fibrose Cística/diagnóstico , Testes de Função Respiratória , Sociedades Médicas , Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/normas , Europa (Continente) , Humanos , Lactente , Avaliação de Resultados em Cuidados de Saúde/métodos , Gravidade do Paciente , Testes de Função Respiratória/métodos , Testes de Função Respiratória/normasAssuntos
Fibrose Cística/complicações , Ceratodermia Palmar e Plantar/etiologia , Criança , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Feminino , Humanos , Imersão/efeitos adversos , Ceratodermia Palmar e Plantar/diagnóstico , Água/efeitos adversosAssuntos
Antibacterianos/uso terapêutico , Fibrose Cística/imunologia , Fibrose Cística/microbiologia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/imunologia , Pseudomonas aeruginosa/imunologia , Criança , Pré-Escolar , Fibrose Cística/epidemiologia , Humanos , Lactente , Infecções por Pseudomonas/epidemiologia , Fatores de Risco , Resultado do TratamentoRESUMO
PURPOSE: The aim of this study was to assess the incidence of late onset complications of totally implantable venous access devices (TIVAD) in patients with cystic fibrosis (CF) and to investigate possible associations between the rate of complications and different policies of TIVAD management. METHODS: A multicenter prospective cohort study was performed in 11 Italian CF Centers. Patients with CF and a TIVAD were recruited and followed-up. RESULTS: The study commenced on May 2008 and ended on September 2010. Eighty subjects were studied (77.5% women--mean age 27.2 years). Eighteen late complications of ports were observed (22.5%; incidence 0.96 per 1000 days of observation): three lumen occlusions, seven catheter-related infections , three port-related venous thrombosis, in addition to five other complications. A statistically significant association was found between the onset of catheter-related infection and the presence of CF-related diabetes (CFRD) (P=.0064) CONCLUSIONS: Our data suggest that TIVADs represent a safe and effective device for the intermittent IV administration of drugs in people with CF. However, people with CFRD have a higher risk of developing TIVAD-related infection.
Assuntos
Obstrução do Cateter , Infecções Relacionadas a Cateter/epidemiologia , Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/instrumentação , Cateteres de Demora , Cateteres Venosos Centrais , Fibrose Cística/complicações , Trombose Venosa Profunda de Membros Superiores/epidemiologia , Adulto , Infecções Relacionadas a Cateter/diagnóstico , Fibrose Cística/tratamento farmacológico , Desenho de Equipamento , Feminino , Humanos , Incidência , Itália/epidemiologia , Masculino , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Trombose Venosa Profunda de Membros Superiores/diagnóstico , Adulto JovemRESUMO
BACKGROUND: The identification of cystic fibrosis (CF) patients who are at greater risk of lung damage could be clinically valuable. Thus, we attempted to replicate previous findings and verify the possible association between three single nucleotide polymorphisms (SNPs c.-52G>A, c.-44C>G and c.-20G>A) in the 5' untranslated region (5' UTR) of the ß defensin 1 (DEFB1) gene and the CF pulmonary phenotype. METHODS: Genomic DNA from 92 Italian CF patients enrolled in different regional CF centres was extracted from peripheral blood and genotyped for DEFB1 SNPs using TaqMan(®) allele specific probes. In order to avoid genetic confounding causes that can account for CF phenotype variability, all patients were homozygous for the F508del CFTR mutation, and were then classified on the basis of clinical and functional data as mild lung phenotype (Mp, n=50) or severe lung phenotype patients (Sp, n=42). RESULTS: For the c.-20G>A SNP, the frequency of the A allele, as well as the AA genotype, were significantly more frequent in Mp than in Sp patients, and thus this was associated with a protective effect against severe pulmonary disease (OR=0.48 and 0.28, respectively). The effect of the c.-20G>A A allele is consistent with a recessive model, and the protective effect against Sp is exerted only when it is present in homozygosis. For the other two SNPs, no differences were observed as allelic and genotypic frequency in the two subgroups of CF patients. CONCLUSIONS: Our results, although necessary to be confirmed in larger and multiethnic populations, reinforce DEFB1 as a candidate modifier gene of the CF pulmonary phenotype.
Assuntos
Regiões 5' não Traduzidas , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/genética , Mutação , beta-Defensinas/genética , Adulto , Feminino , Genótipo , Homozigoto , Humanos , Itália , Masculino , Fenótipo , Polimorfismo Genético , Adulto JovemAssuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/epidemiologia , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/epidemiologia , Fibrose Cística/complicações , Humanos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Índice de Gravidade de DoençaRESUMO
Although maintaining a distance of 1 m between persons with cystic fibrosis (CF) is a universal recommendation to prevent respiratory cross-infections such as Pseudomonas aeruginosa, evidence supporting this preventive measure is scarce. Examining 336 samples from 42 patients with CF collected experimentally from sterile surfaces after speaking and coughing, we found that transmission of P aeruginosa beyond 1 m is possible during both talking and coughing, although the probability is low (1.7%).
Assuntos
Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/transmissão , Fibrose Cística/complicações , Infecções por Pseudomonas/prevenção & controle , Infecções por Pseudomonas/transmissão , Pseudomonas aeruginosa/isolamento & purificação , Adolescente , Adulto , Feminino , Humanos , Controle de Infecções/métodos , Masculino , Medição de Risco , Adulto JovemRESUMO
BACKGROUND: The periodic administration of positive airway pressure combined with directed cough could aid mucus clearance in patients with cystic fibrosis (CF) and severe airway obstruction. OBJECTIVE: To compare the short-term effect of positive expiratory pressure (PEP) physiotherapy via mask (mask PEP), continuous positive airway pressure (CPAP), and noninvasive positive-pressure ventilation (NPPV) physiotherapies on amount of sputum collected. METHODS: Directed cough was standardized for each patient and used as the control treatment. We studied 17 patients with CF (mean +/- SD age 28 +/- 7 y) and severe airway obstruction (forced expiratory volume in the first second 25 +/- 6% of predicted) admitted for pulmonary exacerbation. Mask PEP, CPAP, NPPV, and the control treatment (directed cough) were administered in a random sequence. Each patient received each treatment twice a day (in 70-min sessions) for 2 consecutive days. We measured the wet and dry weight of sputum collected and the number of directed and spontaneous coughs during each session. Spirometry and pulse oximetry were conducted before and after each session. For mask PEP, CPAP, and NPPV, each patient gave a subjective score for the efficacy and tolerability of the treatment, compared to the control treatment. RESULTS: There was no statistically significant difference in the dry weight of sputum collected: mask PEP 0.9 +/- 0.6 g, CPAP 0.8 +/- 0.4 g, NPPV 0.9 +/- 0.6 g, control treatment 1.0 +/- 0.8 g. There was a statistically significant difference in the wet weight of sputum collected: mask PEP 15.8 +/- 5.5 g, CPAP 13.7 +/- 5.5 g, NPPV 13.2 +/- 5.0 g, control treatment 14.0 +/- 5.0 g (p < 0.05), but that difference became nonsignificant when we took into account the number of spontaneous coughs. There were no statistically significant changes in the spirometry and pulse-oximetry values. The patients' subjective efficacy scores were similar for mask PEP, CPAP, and NPPV. Less fatigue was reported after NPPV and CPAP than after mask PEP. CONCLUSIONS: There were no differences in sputum clearance or pulmonary-function measures between mask PEP and short-term administration of either CPAP or NPPV combined with directed cough. After mask PEP these patients felt more tired than after CPAP or NPPV secretion-clearance therapy.