Reversal of cylindrical bronchial dilatations in a subset of adults with cystic fibrosis treated with elexacaftor-tezacaftor-ivacaftor.

BACKGROUND: This study sought to evaluate the impact of elexacaftor-tezacaftor-ivacaftor (ETI) on lung structural abnormalities in adults with cystic fibrosis (awCF) with a specific focus on the reversal of bronchial dilatations. METHODS: Chest computed tomography (CT) performed prior to, and ≥12 months after initiation of ETI were visually reviewed for possible reversal of bronchial dilatations. AwCF with and without reversal of bronchial dilatation (the latter served as controls with 3 controls per case) were selected. Visual Brody score, bronchial and arterial diameters, and lung volume were measured on CT. RESULTS: Reversal of bronchial dilatation was found in 12/235 (5%) awCF treated with ETI. Twelve awCF with and 36 without reversal of bronchial dilatations were further analyzed (male=56%, mean age=31.6±8.5 years, F508del/F508del CFTR =54% and mean %predicted forced expiratory volume in 1 s=58.8%±22.3). The mean±sd Brody score improved overall from 79.4±29.8 to 54.8±32.3 (p<0.001). Reversal of bronchial dilatations was confirmed by a decrease in bronchial lumen diameter in cases from 3.9±0.9 mm to 3.2±1.1 mm (p<0.001), whereas it increased in awCF without reversal of bronchial dilatation (from 3.5±1.1 mm to 3.6±1.2 mm, p=0.002). Reversal of bronchial dilatations occurred in cylindrical (not varicose or saccular) bronchial dilatations. Lung volumes decreased by -6.6±10.7% in awCF with reversal of bronchial dilatation but increased by +2.3±9.6% in controls (p=0.007). CONCLUSION: Although bronchial dilatations are generally considered irreversible, ETI was associated with reversal, which was limited to the cylindrical bronchial dilatations subtype, and occurred in a small subset of awCF. Initiating ETI earlier in life may reverse early bronchial dilatations.

The French Compassionate Program of elexacaftor-tezacaftor-ivacaftor in people with cystic fibrosis with advanced lung disease and no F508del CFTR variant.

BACKGROUND: The European Medicines Agency has approved the cystic fibrosis transmembrane conductance regulator (CFTR) modulator combination elexacaftor-tezacaftor-ivacaftor (ETI) for people with cystic fibrosis (pwCF) carrying at least one F508del variant. The United States Food and Drug Administration (FDA) also approved ETI for pwCF carrying one of 177 rare variants. METHODS: An observational study was conducted to evaluate the effectiveness of ETI in pwCF with advanced lung disease that were not eligible to ETI in Europe. All patients with no F508del variant and advanced lung disease (defined as having a percent predicted forced expiratory volume (ppFEV1)<40 and/or being under evaluation for lung transplantation) and enrolled in the French Compassionate Program initiated ETI at recommended doses. Effectiveness was evaluated by a centralized adjudication committee at 4-6 weeks in terms of clinical manifestations, sweat chloride concentration and ppFEV1. RESULTS: Among the first 84 pwCF included in the program, ETI was effective in 45 (54%) and 39 (46%) were considered to be non-responders. Among the responders 22/45 (49%) carried a CFTR variant that is not currently approved by FDA for ETI eligibility. Important clinical benefits, including suspending the indication for lung transplantation, a significant decrease in sweat chloride concentration by a median [IQR] -30 [-14;-43]mmol·l-1 (n=42; p<0.0001) and an improvement in ppFEV1 by+10.0 [6.0; 20.5] (n=44, p<0.0001), were observed in those for whom treatment was effective. CONCLUSION: Clinical benefits were observed in a large subset of pwCF with advanced lung disease and CFTR variants not currently approved for ETI.

Acneiform Eruption Following Elexacaftor-Tezacaftor-Ivacaftor Treatment in Patients With Cystic Fibrosis.

Importance: A new treatment for cystic fibrosis combining 3 CFTR modulators-elexacaftor (ELX), tezacaftor (TEZ), and ivacaftor (IVA)-has recently been approved for cystic fibrosis treatment. The cutaneous adverse effects following treatment with this combination are poorly described in the literature. Objective: To describe the clinicopathological features and treatment response of ELX-TEZ-IVA-associated acneiform eruptions in patients with cystic fibrosis. Design, Setting, and Participants: This case series study was conducted in the Dermatology Department of Cochin Hospital, Paris, France, from July 2021 to June 2022 in collaboration with the Cochin Reference Center for Cystic Fibrosis. Referred patients were examined by senior dermatologists. All patients with cystic fibrosis treated with ELX-TEZ-IVA and referred for an acneiform rash were included. Exposures: Treatment with ELX-TEZ-IVA. Main Outcomes and Measures: Onset of acneiform rash, type of lesions, and degree of severity, as well as treatments initiated and response, were evaluated. When performed, skin biopsies were reviewed. Results: This study included 16 patients (11 women [68.7%]) with a median (range) age of 27 (22-38) years. Six patients (37.5%) developed new-onset acneiform rashes, whereas 10 patients (62.5%) had a relapse (5 patients) or worsening (5 patients) of previous acne. The median (range) onset of acneiform rash was 45 (15-150) days. At inclusion, 11 patients (68.7%) had facial hyperseborrhea, 15 patients (93.7%) had noninflammatory lesions, and 14 (87.5%) had inflammatory lesions of seborrheic regions. Four patients (25.0%) had severe acne with deep inflammatory lesions and pitted scars. A specific pathological pattern of necrotizing infundibular crystalline folliculitis was observed in 4 patients. Topical acne treatments, antibiotics, and isotretinoin were used successfully in these patients, resulting in partial or complete remission in 12 patients (85.7% of patients reevaluated). Conclusions and Relevance: This case series study found that acneiform eruption is an adverse event associated with ELX-TEZ-IVA treatment in patients with cystic fibrosis. Most patients developed mild lesions. However, isotretinoin treatment may be necessary in some patients. The mechanism of ELX-TEZ-IVA-associated acneiform eruption is currently unknown, but the observation of necrotizing infundibular crystalline folliculitis in biopsied patients may guide further exploration.

Novel radiomics evaluation of bone formation utilizing multimodal (SPECT/X-ray CT) in vivo imaging.

Although an extensive research is being undertaken, the ideal bone graft and evaluation method of the bone formation draw still a warranted attention. The purpose of this study was to develop a novel multimodal radiomics evaluation method, utilizing X-ray computed tomography (CT) and single photon emission computed tomography (SPECT) with Tc-99m-Methyl diphosphonate (Tc-99m-MDP) tracer. These modalities are intended to provide quantitative data concerning the mineral bone density (after evaluation it is referred to as opacity) and the osteoblast activity, at the same time. The properties of bone formation process within poly (methyl methacrylate)-based bone cement graft (PMMA) was compared to that of albumin coated, sterilized, antigen-extracted freeze-dried human bone grafts (HLBC), in caudal vertebrae (C5) of rats. The animals were scanned at 3 and 8 weeks after surgery. In both groups, the mean opacity increased, while the mean Tc-99m-MDP activity decreased. The later parameter was significant (n = 4, p = 0.002) only in HLBC group. The linear regression analysis of PMMA-treated group variables (mean opacity increase; mean Tc-99m-MDP activity decrease), revealed a negative correlation with the medium strength (r = 0.395, p = 0.605). Whereas, it showed strong positive correlation when HLBC group variables were analyzed (r = 0.772, p = 0.012). These results indicate that using HLBC grafts is advantageous in terms of the osteoblast activity and bone vascularization over PMMA cement. Using this regression analysis method, we were able to distinguish characteristics that otherwise could not be distinguished by a regular data analysis. Hence, we propose utilizing this novel method in preclinical tests, and in clinical monitoring of bone healing, in order to improve diagnosis of bone-related diseases.

A prospective analysis of unplanned patient-initiated contacts in an adult cystic fibrosis centre.

BACKGROUND: Timely response should be provided when patients contact the cystic fibrosis (CF) centre in between scheduled visits. Little data exist on unplanned patient-initiated contacts in CF adults. METHODS: A two-stage prospective study was undertaken from 1 January to 31 December 2015 at Cochin Hospital, Paris (France). The first stage included all adults (≥18 years) who initiated unplanned contacts to the CF centre over four months. Four physicians and three nurses systematically recorded unplanned patient-initiated contacts. The data was analysed to determine why and how patients contacted the CF centre and time spent responding to their request(s). The second stage (one physician, three nurses) lasted twelve months and explored whether high contact frequency was associated with disease severity, using multivariate logistic regression. RESULTS: In the first stage, 259 of 410 patients (63%) initiated at least one unplanned contact, corresponding to 1067 contacts over 4 months. Patients favoured email with physicians (61% of contacts) and telephone with nurses (87% of contacts). Total time spent by the 7 caregivers on providing responses was 8 h/work week. Reasons for contacting the CF centre varied greatly, but <20% of contacts were directly related to symptom management. In the second stage, 180 of 212 patients (85%) initiated 1876 contacts over 12 months. Factors associated with ≥5 contacts/year were female sex, FEV1 ≤ 30% predicted, ≥5 physician visits/year, and ≥ 1 hospital admission/year. CONCLUSIONS: Answering unplanned patient-initiated contacts represented a significant workload for CF caregivers. Increased disease severity was associated with high contact frequency.

Real-life initiation of lumacaftor/ivacaftor combination in adults with cystic fibrosis homozygous for the Phe508del CFTR mutation and severe lung disease.

OBJECTIVE: To investigate the short-term adverse events and effectiveness of lumacaftor/ivacaftor combination treatment in adults with cystic fibrosis (CF) and severe lung disease in a real life setting. METHODS: A multicentre observational study investigated adverse events, treatment discontinuation, FEV1 and body mass index (BMI) one month and three months after lumacaftor/ivacaftor initiation in adults with CF and FEV1 below 40% predicted. RESULTS: Respiratory adverse events (AEs) were reported by 27 of 53 subjects (51%) and 16 (30%) discontinued treatment. The mean absolute change in FEV1 was +2.06% after one month of treatment (P=0.086) and +3.19% after 3 months (P=0.009). BMI was unchanged. CONCLUSIONS: Treatment with lumacaftor/ivacaftor in patients with CF and severe lung disease was discontinued more frequently than reported in clinical trials, due to respiratory AEs. Nevertheless, the patients who continued treatment had an increase in lung function comparable to what was observed in pivotal trials.

CFTR and/or pancreatitis susceptibility genes mutations as risk factors of pancreatitis in cystic fibrosis patients?

BACKGROUND/OBJECTIVES: Currently, factors that promote the occurrence of pancreatitis episodes in patients affected with cystic fibrosis (CF) and pancreatic sufficiency (PS) are largely unknown. METHODS: Six genes involved in pancreatitis or in ion transport into the pancreatic duct were investigated by next generation sequencing in 59 adult CF-PS patients with two identified CF mutations. Data on predisposing environmental factors were also recorded. RESULTS: 19 experienced at least one episode of acute pancreatitis (AP) (AP+) and 40 patients did not (AP-). No influence of environmental factor was evidenced. No specific CFTR genotype was found predictive of pancreatitis. Patients sharing the same CFTR genotype may or may not experience AP episodes. Frequent and rare missense variants were found in 78.9% patients in group AP+ and 67.5% in group AP- but a few of them were pathogenic. CONCLUSIONS: AP or recurrent AP (RAP) is a frequent complication in our series of adult CF-PS patients. The majority of mild CFTR mutations found in group AP+ were located in the first transmembrane region. No clear other genetic factor could be found predictive of AP/RAP. Further experiments in large homogenous cohorts of CF-PS patients, including whole genome sequencing, may identify genetic predisposing factors to pancreatitis.

Renin-associated hypertension after bronchial artery embolization in cystic fibrosis.

Bronchial artery embolization is the recommended therapy for massive hemoptysis in patients with cystic fibrosis (CF). We report on two cases of multiple renal infarcts and renin-associated hypertension and hypokalemia occurring in CF adults after bronchial artery embolizations. These complications were presumably related to crossing of small calibrated microspheres through arteriovenous anastomoses. Although hypokalemia resolved rapidly, hypertension persisted at least 6 months and its control required multiple antihypertensive agents. Physicians should be aware of this potentially severe, but previously unreported, complication of bronchial artery embolization.

Causes of death in French cystic fibrosis patients: The need for improvement in transplantation referral strategies!

BACKGROUND: Little data exist on causes of death in cystic fibrosis (CF) patients in the era of lung transplantation. METHODS: Deaths in CF patients in France (2007-2010) were identified using the French CF Registry and causes of deaths were determined based on medical files by a mortality adjudication committee. RESULTS: Of 256 deaths, half occurred after lung transplantation and were related to early or late complications of transplantation, whereas half occurred in patients who did not receive lung transplantation and were primarily related to respiratory failure or massive hemoptysis. Among patients who did not receive lung transplantation, only 19% died while waiting on a lung transplantation list. Lack of listing for lung transplantation was primarily related to late, or to lack of transplantation referral, rather than to contraindication to transplantation. CONCLUSIONS: These data suggest that improvement in transplantation referral strategies may result in transplantation-related survival benefits.

DCTN4 as a modifier of chronic Pseudomonas aeruginosa infection in cystic fibrosis.

BACKGROUND AND AIMS: Pseudomonas aeruginosa (Pa) infection in cystic fibrosis (CF) patients is associated with worse long-term pulmonary disease and shorter survival, and chronic Pa infection (CPA) is associated with reduced lung function, faster rate of lung decline, increased rates of exacerbations and shorter survival. By using exome sequencing and extreme phenotype design, it was recently shown that isoforms of dynactin 4 (DCTN4) may influence Pa infection in CF, leading to worse respiratory disease. The purpose of this study was to investigate the role of DCTN4 missense variants on Pa infection incidence, age at first Pa infection and chronic Pa infection incidence in a cohort of adult CF patients from a single centre. METHODS: Polymerase chain reaction and direct sequencing were used to screen DNA samples for DCTN4 variants. RESULTS: A total of 121 adult CF patients from the Cochin Hospital CF centre have been included, all of them carrying two CFTR defects: 103 developed at least 1 pulmonary infection with Pa, and 68 patients of them had CPA. DCTN4 variants were identified in 24% (29/121) CF patients with Pa infection and in only 17% (3/18) CF patients with no Pa infection. Of the patients with CPA, 29% (20/68) had DCTN4 missense variants vs 23% (8/35) in patients without CPA. Interestingly, p.Tyr263Cys tend to be more frequently observed in CF patients with CPA than in patients without CPA (4/68 vs 0/35), and DCTN4 missense variants tend to be more frequent in male CF patients with CPA bearing two class II mutations than in male CF patients without CPA bearing two class II mutations (P = 0.06). CONCLUSIONS: Our observations reinforce that DCTN4 missense variants, especially p.Tyr263Cys, may be involved in the pathogenesis of CPA in male CF.

Reduced risk of nontuberculous mycobacteria in cystic fibrosis adults receiving long-term azithromycin.

BACKGROUND: Azithromycin reduces exacerbations in cystic fibrosis (CF) patients. Our aim was to investigate its association with nontuberculous mycobacteria isolation and macrolide susceptibility. METHODS: From 2006 to 2010, all adult CF subjects at Cochin Hospital (Paris, France) harboring at least one positive NTM isolate were identified (Cases). In a nested case-control study, each Case was individually matched for age and gender with up to 4 CF adults with no NTM isolate (Controls). Clinical data at the time of first NTM isolate (index date) in Cases were compared with those of Controls using multivariate conditional regression analysis. RESULTS: CF subjects with positive NTM isolates (Cases, n=41) were matched to 155 Controls. Among Cases, 48.7% had isolates from Mycobacterium avium complex and 58.5% from Mycobacterium abscessus complex, and 31 Cases fulfilled the 2007 American Thoracic Society criteria for NTM infection (ATS+ Cases). Cases and ATS+ Cases were more likely to have low body mass index and colonization with Aspergillus fumigatus. Azithromycin was associated with a two-fold reduction in NTM isolates. Only one M. avium complex isolate had acquired macrolide resistance. CONCLUSION: These data suggest that azithromycin is a primary prophylaxis for NTM infection in CF adults.

Complications of peripherally inserted central catheters in adults with cystic fibrosis or bronchiectasis.

BACKGROUND: Peripherally inserted central catheters (PICCs) are increasingly used in patients with cystic fibrosis (CF) or with non-CF bronchiectasis, but little data exist on catheter-related complications in this setting. METHODS: Prospective follow-up of consecutive PICCs inserted for intravenous (IV) antibiotics in adults with CF or with non-CF bronchiectasis at Cochin Hospital (Paris, France). RESULTS: Between March 2009 and December 2011, 182 PICCs were prescribed in 117 adults (67 CF and 50 non-CF patients). Ultrasound-guided placement of catheter was successful in 174/182 (95.6%) procedures; no insertion complication occurred. The mean ± SD catheter dwell time was 15 ± 9 days. No catheter-associated bloodstream infection occurred; main complications were symptomatic upper limb deep vein thrombosis (2%), catheter obstruction (18%) and persistent pain after catheter insertion (18%). Patients' satisfaction was high and PICC could be used to perform antibiotic courses in most patients. CONCLUSIONS: PICCs were generally safe for performing IV antibiotic courses in patients with CF or non-CF bronchiectasis, but prolonged pain and/or catheter obstruction occurred in approximately 20% of cases.

Prognostic value of six minute walk test in cystic fibrosis adults.

BACKGROUND: The 6 min walk test (6MWT) provides prognostic information in various respiratory diseases, but limited data exist in cystic fibrosis (CF) adults. METHODS: Consecutive CF adults who performed 6MWT at Cochin Hospital (Paris, France) over 12 years were analyzed. The cut-off 6 min walking distance (6MWD) value that best predicted a combined endpoint (death without transplant or lung transplant) was established using a receiver operating curve. Determinants of low 6MWD or of desaturation (SpO2 ≤ 90%) during 6MWT were examined using multivariate logistic regressions. Prognostic value of these variables was assessed using Kaplan-Meier and Cox analyses. RESULTS: 6MWT was performed in 286 CF adults (median: age, 28 yr; FEV1, 45% predicted) of whom 14% (n = 40) had lung transplant and 6% (n = 18) died without transplant. 6MWD correlated with FEV1% predicted (r = 0.43; P < 0.001), but markedly differed in subjects within the same range of FEV1. A 6MWD ≤ 475 m predicted death or transplant and was mostly found in patients with FEV1 ≤ 60% predicted. Desaturation during the 6MWT occurred in 29% of patients, exclusively in subjects with FEV1 ≤ 60% predicted. Both 6MWD ≤ 475 m and desaturation during the 6MWT were independent predictors of death or transplant. CONCLUSION: The 6MWT provides prognostic information in CF adults, especially in subjects with FEV1 ≤ 60% predicted.

Outcome of cystic fibrosis-related diabetes two years after lung transplantation.

BACKGROUND: Although transplantation is known to impair glucose tolerance, evolution of pre-existing diabetes after lung transplantation (LT) in cystic fibrosis (CF) has never been described. OBJECTIVES: We aimed to assess the outcome of CF-related diabetes (CFRD) after LT, with the hypothesis that suppressing chronic inflammatory foci may improve glucose tolerance in some patients. METHODS: In a retrospective study of 29 CF diabetic patients treated with insulin and undergoing LT, CFRD control was assessed 3 months before LT and 1 (n = 27) and 2 (n = 18) years after LT by measuring insulin dosage, fasting blood glucose and glycosylated hemoglobin (HbA1c) levels. Patients with HbA1c ≤7% and an insulin dose ≤1 UI/kg/day were defined as having controlled CFRD (group A). Other patients were assigned to group B. RESULTS: Before LT, 19 (65.5%) patients were in group A. At 2 years, 6 of 10 (60%) patients who were in group B prior to LT had moved into group A, which then comprised 77.8% of all patients. Insulin could have been stopped in 5 patients. Uncontrolled CFRD before LT (OR = 16) and a long delay between the diagnosis of CFRD and LT (OR = 1.3) were significant predictors of uncontrolled CFRD at 1 year. CONCLUSIONS: LT does not seem to worsen CFRD in some patients, suggesting that in some cases, glucose tolerance may be improved by the suppression of chronic pulmonary infection.

High prevalence of azole-resistant Aspergillus fumigatus in adults with cystic fibrosis exposed to itraconazole.

Aspergillus fumigatus is the most frequent fungus found in the sputum of cystic fibrosis (CF) subjects. Itraconazole is prescribed for allergic bronchopulmonary aspergillosis (ABPA) or Aspergillus bronchitis in CF subjects. We hypothesized that A. fumigatus isolates in the sputum of CF subjects with previous exposure to itraconazole was associated with higher prevalence of azole resistance. From June 2010 to April 2011, sputum samples from adult CF subjects at Cochin University Hospital (France) were examined systematically for the detection of A. fumigatus. MICs of A. fumigatus isolates against azoles were screened using Etest, and reduced susceptibility to azoles was confirmed using the CLSI broth microdilution method. A. fumigatus was isolated from the sputum of 131/249 (52.6%) adult CF subjects, and 47/131 (35.9%) subjects had received previous treatment with itraconazole. Reduced A. fumigatus susceptibility to itraconazole (MIC, ≥2 mg/liter) was confirmed in 6/131 (4.6%) subjects. All 6 isolates also had reduced susceptibility to posaconazole (MIC, ≥0.5 mg/liter), and 3/6 isolates had reduced susceptibility to voriconazole (MIC, ≥2 mg/liter). Mutations in the cyp51A gene were detected at positions previously implicated to cause resistance in 5 isolates. Azole-resistant A. fumigatus isolates were found in 5/25 (20%) subjects exposed to itraconazole within the previous 3 years. High rates of azole-resistant A. fumigatus isolates were present in adult CF subjects and were associated with recent itraconazole exposure. Although the clinical implications of these findings will require further studies, the cautious use of itraconazole in adult CF subjects can be recommended.

Employment and work disability in adults with cystic fibrosis.

BACKGROUND: As a result of prolonged survival, more patients with cystic fibrosis (CF) participate in the labour force. The aim of this study was to evaluate their education, occupation levels and risk factors for work disability. METHOD: 207 patients answered a self-administered questionnaire about their educational level and work status. Independently, medical records were reviewed for illness severity indicators. RESULTS: 39 patients (19%) were students, 117 (57%) were in the labour force, 13 (6%) were seeking employment and 38 (18%) were inactive. CF patients had a higher educational level and were more likely to hold skilled jobs and to work part time than the general population. FEV1 and educational level were the strongest predictive factors of disability. CONCLUSION: Many CF patients have access to professional life. Their higher educational levels improve the chances of attaining employment, which highlights the need for career counselling. Working part time helps to maintain employment despite declining health.

Liver disease in adult patients with cystic fibrosis: a frequent and independent prognostic factor associated with death or lung transplantation.

BACKGROUND & AIMS: Increased life expectancy in patients with cystic fibrosis (CF) allows better knowledge of non-pulmonary complications like liver disease (CFLD). However, few data have been published in large adult cohorts. The aim of this study was to estimate the prevalence and the prognosis of CFLD in adult CF patients. METHODS: A retrospective analysis of a monocentric cohort of adult CF patients prospectively followed, at least every year, was performed. CFLD was diagnosed using published composite criteria. If cirrhosis was suspected, upper digestive endoscopy was realized to assess the presence of portal hypertension. RESULTS: A cohort of 285 adult CF patients was followed during 4.8 ± 3.6 years. Among them, 90 had CFLD at the beginning of follow-up and 23 a suspicion of cirrhosis. Factors independently associated with liver disease at baseline were history of meconium ileus, pancreatic insufficiency, chronic colonization with Burkholderia cepacia and the number of IV antibiotic courses per year. Nine patients developed liver decompensation during follow-up, all with a suspicion of cirrhosis at baseline. Six patients underwent liver transplantation alone and three patients combined liver and lung transplantation. Factors independently associated with death or lung transplantation at baseline were liver disease, BMI, forced expiratory volume in 1 second and number of IV antibiotic courses per year. CONCLUSIONS: CFLD was present at baseline in one third of adult patients with CF with a marked risk of liver decompensation during follow-up. Moreover, CFLD at baseline appears as an independent factor associated with death or lung transplantation.

Smoking practices in Jordanian people and their impact on semen quality and hormonal levels among adult men.

Despite worldwide anti-smoking campaigns, cigarette smoking prevalence is increasing in the third-world countries. It is now regarded as the most important public health issue. Here, we study the current smoking situation and investigate the impact of cigarette smoking on semen quality and hormonal levels among adult people. Furthermore, we suggest various strategies to reduce smoking consumption among young individuals. Across-sectional data from 804 adult smoker subjects (male n = 530 and female n = 274) aged between 15 and 45 years were analyzed. One hundred and eleven males were agreed for further evaluation of their semen quality and hormones compared with 93 age-matched non-smoking males. This study showed that the majorfactors initiating smoking among women were friends' influence (49%), life pressures (16%) and parental imitation (14%). The major reasons in men was friends' influence (65%). Furthermore, 61% ofwomen and 89% of men smoke in public implying social acceptance oreven encouragement of this habit. This study also found that low-income Jordanians consume more tobacco materials than those in the middle- and higher income. Furthermore, smokers had significantly lower (p < 0.001) sperm concentration and motility values and higher (p < 0.001) serum testosterone and luteinizing hormone (LH) levels than non-smokers.