Pulmonary functions, nasal symptoms, and quality of life in patients with primary ciliary dyskinesia (PCD).

BACKGROUND: Several factors may influence quality of life (QOL) for patients with primary ciliary dyskinesia (PCD). We aimed to evaluate the association between pulmonary functions, nasal symptoms and QOL in PCD patients. METHODS: A prospective single center study. Patients performed spirometry, whole body plethysmography, forced oscillation technique (FOT), lung clearance index (LCI), 6-min walk test (6MWT), and filled two questionnaires: a specific PCD QOL questionnaire (PCD-QOL) and Sino-nasal outcome test (SNOT-22) questionnaire, assessing symptoms of chronic rhinosinusitis and health related QOL. RESULTS: Twenty-seven patients (56% females), age 19.4 ± 10.5 years were included; their, FEV1 was 74.6 ± 22.7%, and RV/TLC was (157.3 ± 39.3% predicted). Health perception and lower respiratory symptoms domains of PCD-QOL had the lowest score (median [IQR]: 50 [33.3-64.6] and 57.1 [38.9-72.2], respectively). FOT parameters correlated with several PCD-QOL domains. R5 z-score (indicating total airway resistance) and AX z-score (indicating airway reactance) correlated negatively with physical domain (r = -0.598, p = .001, and r = -0.42, p = .03, respectively); R5 z-score also correlated negatively with hearing domain (r = -0.57, p = .002). R5-20 z-score (indicating small airway resistance) correlated negatively with role domain (r = -0.49, p = .03). SNOT-22 score correlated negatively with several PCD-QOL domains (lower respiratory symptoms r = -0.77, p < .001; physical r = -0.72, p < .001; upper respiratory symptoms r = -0.66, p < .001). No correlations were found between spirometry values, LCI, 6MWT, and PCD-QOL. CONCLUSIONS: FOT suggested small airway dysfunction, and correlated negatively with several PCD-QOL domains. Nasal symptoms had strong negative correlations with PCD-QOL. Larger longitudinal studies will further elucidate factors affecting QOL in PCD.

The effect of inspiratory muscle training in PCD and CF patients: A pilot study.

BACKGROUND: Effective work of breathing and bronchial hygiene requires synergy of inspiratory and expiratory muscles. Inspiratory muscle training (IMT) is a part of pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD). There is some evidence of its efficacy in cystic fibrosis (CF) and, recently, in long COVID-19. We are not aware of studies on IMT in primary ciliary dyskinesia (PCD). Our aim was to assess the effect of IMT on respiratory muscle strength and pulmonary function in PCD and CF patients. METHODS: A single center pilot study. Spirometry, lung clearance index (LCI), maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) were measured at baseline (visit 1), after a month of IMT with ®POWERbreathe (visit 2), and at follow-up (visit 3). RESULTS: The cohort included 27 patients (19 PCD, 8 CF); mean age 18.4 ± 9.8 years. After a month of IMT, there was a significant increase in MIP and MIP% (6.19-7.44, p = .015; and 81.85%-100.41%, p = .046, respectively), which was sustained at visit 3. Compliance ≥90% led to higher improvement in MIP. In sub-group analysis, improvement in MIP and MIP% remained significant for PCD patients (p = .026 and p = .049, respectively). No significant changes were found in spirometry, MEP or LCI. CONCLUSIONS: IMT was well-tolerated and led to improved inspiratory muscle strength in PCD patients. The clinical implication of improved MIP should be further investigated. Larger, long-term studies are needed to evaluate long-term effects of IMT on pulmonary function, respiratory muscle strength, pulmonary exacerbations, and quality of life.

The effect of nose clip on exercise-induced bronchoconstriction in adolescents.

BACKGROUND: Oral breathing is considered to increase hyper-responsiveness of the airways. Data on the need for nose clip (NC) during exercise challenge test (ECT) in children and adolescents is scarce. Ouraim was to evaluate the role of NC during ECT in children and adolescents. METHODS: A prospective, cohort study; children referred for ECT were evaluated on two separate visits, with and without a NC. Demographic, clinical data and measurements of lung functions were recorded. Allergy and asthma control were evaluated by Total Nasal Symptoms Score (TNSS) and Asthma Control Test (ACT) questionnaires. RESULTS: Sixty children and adolescents (mean age 16.7 ± 1.1 years, 38% Female,) performed ECT with NC and 48 (80%) completed visit 2 (ECT without NC), 8.7 ± 7.9 days after visit 1. Following exercise, 29/48 patients (60.4%) with NC had a decline of ≥12% in forced expiratory volume in the first second (FEV1 ) (positive ECT) compared to only 16/48 (33.3%) positive tests without NC (p = 0.0008). Test result was changed in 14 patients from positive ECT (with NC) to negative ECT (no NC) and in only one patient from negative to positive. The use of NC resulted in greater FEV1 decline (median 16.3% predicted, IQR 6.0-19.1% predicted vs. median 4.5% predicted, IQR 1.6-18.4% predicted, p = 0.0001), and better FEV1 increase after bronchodil at or inhalation compared to ECT without NC. Higher TNSS scores did not predict higher probability to positive ECT. CONCLUSIONS: The use of NC during ECT increases detection rate of exercise induced bronchoconstriction during ECT in the pediatric population. These findings strengthen the recommendation of nasal blockage during ECT in children and adolescents.

Significant exercise limitations after recovery from MIS-C related myocarditis.

BACKGROUND: Myocarditis is one of the presentations of multisystemic inflammatory syndrome in children (MIS-C) following coronavirus disease 2019 (COVID-19). Although the reported short-term prognosis is good, data regarding medium-term functional capacity and limitations are scarce. This study aimed to evaluate exercise capacity as well as possible cardiac and respiratory limitations in children recovered from MIS-C related myocarditis. METHODS: Fourteen patients who recovered from MIS-C related myocarditis underwent spirometry and cardiopulmonary exercise testing (CPET), and their results were compared with an age-, sex-, weight- and activity level-matched healthy control group (n = 14). RESULTS: All participants completed the CPET with peak oxygen uptake (peak [Formula: see text]), and the results were within the normal range (MIS-C 89.3% ± 8.9% and Control 87.9% ± 13.7% predicted [Formula: see text]). Five post-MIS-C patients (35%) had exercise-related cardio-respiratory abnormalities, including oxygen desaturation and oxygen-pulse flattening, compared to none in the control group. The MIS-C group also had lower peak exercise saturation (95.6 ± 3.5 vs. 97.6 ± 1.1) and lower breathing reserve (17.4% ± 7.5% vs. 27.4% ± 14.0% of MVV). CONCLUSIONS: Patients who recovered from MIS-C related myocarditis may present exercise limitations. Functional assessment (e.g., CPET) should be included in routine examinations before allowing a return to physical activity in post-MIS-C myocarditis. Larger, longer term studies assessing functional capacity and focusing on physiological mechanisms are needed.

Effect of Trikafta on bone density, body composition and exercise capacity in CF: A pilot study.

BACKGROUND: While the positive effect of Trikafta on cystic fibrosis (CF) pulmonary disease is well established, there is limited data about its effect on bone mineral density (BMD), body composition and exercise capacity. METHODS: A pilot single center study. BMD and body composition were measured three months after the initiation of Trikafta (study group) and compared to values obtained 2 years earlier. CF patients not treated with Trikafta, for whom BMD was measured 2 years apart, served as controls. Spirometry, lung clearance index (LCI), sweat test, six-min walk test (6MWT) and cardio-pulmonary exercise test (CPET) were performed before and three months after the initiation of Trikafta. RESULTS: Nine study patients, aged 18.6 ± 4.7 years, and nine controls. For the study group, BMI and hip and spine BMD increased significantly (19.4 ± 2.6 to 20.3 ± 2.19 BMI, p = 0.05; 0.73 ± 0.098 to 0.81 ± 0.12 gr/cm2 hip, p = 0.017; 0.76 ± 0.14 to 0.82 ± 0.14 gr/cm2 spine, p = 0.025). For the control group, there was no difference in hip or spine BMD. Lean body mass, %fat z-score and fat mass/height2 z-score increased significantly (34770.23 ± 10521.21 to 37430.16 ± 10330.09gr, p = 0.017; -0.8 ± 0.75 to 0.46 ± 0.58, p = 0.012; and -0.98 ± 0.66 to -0.04 ± 0.51, p = 0.025, respectively). 6MWT improved from 541.1 ± 48.9 to 592.9 ± 54.5 m (p = 0.046). As expected, FEV1%pred increased (p = 0.008) and sweat chloride decreased significantly (p = 0.017). In CPET, VE/VCO2 improved, indicating better ventilatory efficiency. CONCLUSIONS: To the best of our knowledge, this is the first study evaluating the metabolic effects of Trikafta. The results are encouraging and offer hope beyond the well-established effect on pulmonary disease. Larger long-term studies are warranted to unpin the underlying physiological mechanisms.

Cardiopulmonary Exercise Testing in Childhood in Late Preterms: Comparison to Early Preterms and Term-Born Controls.

Background: Late preterm (340−366 weeks gestational age [GA]) infants may have abnormal pulmonary development and possible exercise physiology parameters. We aim to assess the effect of late prematurity on exercise capacity in childhood and to compare it to early preterm (EP) (born < 300 GA), and to term healthy control (TC) (>370 week GA). Methods: Late preterm and early preterm (7−10 years) completed a cardiopulmonary exercise test (CPET) and spirometry and were compared to EP and to TC. Results: Eighty-four children (age 9.6 ± 1.0 years, 48% girls) participated. Twenty-one former LP were compared to 38 EP (15 with Bronchopulmonary dysplasia (BPD) [EP+], 23 without BPD [EP−]) and to 25 TC children. Peak oxygen uptake (peakV̇O2) was statistically lower than in the TC, but within the normal range, and without difference from the EP (LP 90.2 ± 15.1%, TC 112.4 ± 16.9%, p < 0.001; EP+ 97.3 ± 25.5%, EP− 85.4 ± 20.8%, p = 0.016 and p < 0.001, respectively, when compared with TC). Lung function (FEV1) was lower than normal only in the EP+ (75.6 ± 14.9% predicted, compared with 12.5 ± 87.8 in EP−, 87.5 ± 16.9 in LP and 91.0 ± 11.7 in TC). Respiratory and cardiac limitations were similar between all four study groups. Conclusions: This study demonstrated lower exercise capacity (peakV̇O2) in former LP children compared with healthy term children. Exercise capacity in LP was comparable to that of EP, with and without BPD. However, the exercise test parameters, specifically peakV̇O2, were within the normal range, and no significant physiological exercise limitations were found.

Functional capacity and quality of life in patients with vascular ring.

BACKGROUND: Vascular rings are congenital anomalies of the aortic arch that compress the trachea and esophagus and may require corrective surgery. Data about the long-term effects of vascular rings are scarce. We aimed to evaluate the long-term cardiorespiratory, exercise capacity, and quality of life of vascular ring patients. METHODS: A single center prospective study evaluating spirometry, echocardiography, six-minute walk test (6MWT), cardiopulmonary exercise testing (CPET), and quality of life questionnaire (SF36) in patients with a diagnosis of vascular ring, with or without corrective surgery. RESULTS: Twenty-seven patients participated (11.9 ± 6 years, 52% males). The most common diagnosis was double aortic arch (16 patients, 59%). Nineteen patients had corrective surgery (O) and 8 did not (NO). Pulmonary function tests were within normal range in both groups (FEV1 % predicted O = 87.6 ± 16.5, NO = 83 ± 10.8%). However, 11/27 had abnormal FEV1 , 5 had abnormal FVC, and 13 (48%) had flattening of the expiratory curve. 6MWD and oxygen uptake were similarly mildly reduced in both groups; (6MWD O = 80.1 ± 10.7% predicted, NO = 74.1 ± 10.9% and oxygen uptake O = 78.5 ± 23.2% predicted, NO = 73.4 ± 14.3%). Peak O2 pulse (V̇O2 /HR% predicted) was mildly reduced in the NO group (O = 88.4 ± 17.3%, NO = 75.8 ± 16.2%). Echocardiogram and SF36 scores were normal in all patients. CONCLUSIONS: Long-term evaluation of patients born with vascular rings revealed mild pulmonary impairment, reduction in 6MWD, and oxygen uptake. The NO group had also mild reduced peak O2 pulse. Larger, long-term studies assessing functional parameters in operated and non-operated patients are needed to assess disease/surgery limitation in patients with vascular rings. Clinical trial registration number: NCT04781738.

The effect of probiotic administration on metabolomics and glucose metabolism in CF patients.

BACKGROUND AND OBJECTIVES: Cystic fibrosis (CF)-related diabetes (CFRD) affects 50% of CF adults. Gut microbial imbalance (dysbiosis) aggravates their inflammatory response and contributes to insulin resistance (IR). We hypothesized that probiotics may improve glucose tolerance by correcting dysbiosis. METHODS: A single-center prospective pilot study assessing the effect of Vivomixx® probiotic (450 billion/sachet) on clinical status, spirometry, lung clearance index (LCI), and quality of life (QOL) questionnaires; inflammatory parameters (urine and stool metabolomics, blood cytokines); and glucose metabolism (oral glucose tolerance test [OGTT]), continuous glucose monitoring [CGM], and homeostasis model assessment of IR (HOMA-IR) in CF patients. RESULTS: Twenty-three CF patients (six CFRD), mean age 17.7 ± 8.2 years. After 4 months of probiotic administration, urinary cysteine (p = 0.018), lactulose (p = 0.028), arabinose (p = 0.036), mannitol (p = 0.041), and indole 3-lactate (p = 0.046) significantly increased, while 3-methylhistidine (p = 0.046) and N-acetyl glutamine (p = 0.047) decreased. Stool 2-Hydroxyisobutyrate (p = 0.022) and 3-methyl-2-oxovalerate (p = 0.034) decreased. Principal component analysis, based on urine metabolites, found significant partitions between subjects at the end of treatment compared to baseline (p = 0.004). After 2 months of probiotics, the digestive symptoms domain of Cystic Fibrosis Questionnaire-Revised improved (p = 0.007). In the nondiabetic patients, a slight decrease in HOMA-IR, from 2.28 to 1.86, was observed. There was no significant change in spirometry results, LCI, blood cytokines and CGM. CONCLUSIONS: Changes in urine and stool metabolic profiles, following the administration of probiotics, may suggest a positive effect on glucose metabolism in CF. Larger long-term studies are needed to confirm our findings. Understanding the interplay between dysbiosis, inflammation, and glucose metabolism may help preventing CFRD.

Functional Capacity in Patients Who Recovered from Mild COVID-19 with Exertional Dyspnea.

BACKGROUND: Post mild COVID-19 dyspnea is poorly understood. We assessed physiologic limitations in these patients. METHODS: Patients with post mild COVID-19 dyspnea (group A) were compared (pulmonary function tests, 6-min walk test (6MWT), echocardiography and cardiopulmonary exercise test (CPET)) to post moderate/severe COVID-19 (group B) and to CPET and spirometry of patients with unexplained dyspnea (group C). RESULTS: The study included 36 patients (13 in A, 9 in B and 14 in C). Diffusion capacity was lower in group B compared to group A (64 ± 8 vs. 85 ± 9% predicted, p = 0.014). 6MWT was normal and similar in both patient groups. Oxygen uptake was higher in group A compared to groups B and C (108 ± 14 vs. 92 ± 13 and 91 ± 23% predicted, p = 0.013, 0.03, respectively). O2 pulse was normal in all three groups but significantly higher in the mild group compared to the control group. Breathing reserve was low/borderline in 2/13 patients in the mild group, 2/9 in the moderate/severe group and 3/14 in the control group (NS). CONCLUSIONS: Patients with post mild COVID-19 dyspnea had normal CPET, similar to patients with unexplained dyspnea. Other mechanisms should be investigated and the added value of CPET to patients with post mild COVID-19 dyspnea is questionable.

4-week daily airway clearance using oscillating positive-end expiratory pressure versus autogenic drainage in bronchiectasis patients: a randomised controlled trial.

BACKGROUND: Airway clearance is a fundamental component of bronchiectasis care. Lung clearance index (LCI) is a measurement of ventilation inhomogeneity. Its responsiveness to long-term airway clearance is unknown. We aimed to compare two methods of daily airway clearance over 4 weeks: autogenic drainage (AD) and oscillating positive airway pressure (oPEP), and to determine effects of airway clearance on LCI and clinical outcomes. METHODS: Adults with bronchiectasis naive to airway clearance were randomised to daily airway clearance with either AD or oPEP. Difference in LCI as primary outcome, spirometry, sputum volume and purulence, and quality of life were at randomisation and after 4 weeks of airway clearance. RESULTS: 51 patients (32 women and 19 men, mean age 66.2±12.8 years) were randomised and 49 completed the study (25 AD and 24 oPEP). The LCI and forced expiratory volume in 1 s did not change between visits between groups (difference between groups 0.02), nor between visits in either group. Sputum quantity decreased in 12 out of 24 (50%) of the oPEP group, and in six out of 25 (24%) of the AD group (p=0.044). The "treatment burden" worsened or was unchanged in 70% of participants randomised to AD and 55% randomised to oPEP (p=0.038). CONCLUSION: Sputum quantity decreased in more participants randomised to oPEP group after 1 month of daily airway clearance, with a better treatment burden. The effects of 4 weeks of airway clearance on LCI were not significant in either treatment group.

Individualized Assessment of Exercise Capacity in Response to Acute and Long-Term Enzyme Replacement Therapy in Pediatric Pompe Disease.

BACKGROUND: Enzyme replacement therapy (ERT) with alglucosidase alfa improves the prospect of patients with infantile-onset Pompe disease (IOPD). However, a progressive decline has been reported. Objective quantification of the response to ERT when assessing newer strategies is warranted. METHODS: This combined retrospective-prospective study assessed the acute and long-term effects of ERT on exercise in IOPD patients. Evaluation included cardiopulmonary exercise testing (CPET), 6-min walking test (6MWT), spirometry, motor function test (GMFM-88) and enzyme blood levels. RESULTS: Thirty-four CPETs (17 pre- and 17 two days-post ERT) over variable follow-up periods were performed in four patients. Two days following ERT, blood enzyme levels increased (median, 1.22 and 10.15 µmol/L/h (p = 0.003)). However, FEV1, FVC and GMFM-88, the median 6MWD and the peak VO2 were unchanged. Long-term evaluations showed stabilization in young patients but progressive deterioration in adolescents. Clinical deterioration was associated with more pronounced deterioration in peak VO2 followed in the decreasing order by 6MWD, FVC and GMFM-88. CONCLUSIONS: The peak VO2 and 6MWD might serve as more sensitive markers to assess clinical deterioration. More studies are needed to clarify the sensitivity of the peak VO2 and 6MWT for quantification of individualized response. This may be important when assessing newer strategies and formulations in IOPD.

Short- and long-term effects of fluticasone furoate/vilanterol in exercising asthmatic adolescents: A randomized and open label trial.

PURPOSE: Relvar® (fluticasone furoate [FF]/vilanterol [VI]) is a once-daily inhaler with bronchodilator effect lasting 24 h. Our aim was to investigate the short- and long-term effects of FF/VI on exercise-induced asthma (EIA) in adolescents. METHODS: Ninety-three adolescent asthmatics aged 12-18 years were referred for evaluation of EIA. Following a positive exercise challenge test (ECT), 22/44 were allocated to a single administration of salbutamol (400 µg) and 22/44 to FF/VI (92/22 µg) in a double-blind method. Thirty-five subjects were reassessed by repeat ECT 30-60 days of FF/VI. RESULTS: Median FEV1 change post-ECT at baseline was -22.8% predicted (interquartile range [IQR] -26.1 and -18.0) for salbutamol and -21.0 (IQR -30.7 and -16.8) for FF/VI. Following bronchodilator, FEV1 improved similarly in both groups. Repeat ECT following 30-60 days of FF/VI resulted in negative ECT in 33/35 subjects; the median decrease in FEV1 of these 35 subjects was 22.6% predicted (IQR 29-18) before, and 4.6% predicted (IQR 8.7-2.5) after 30-60 days of FF/VI treatment (p < 0.0001). CONCLUSIONS: FF/VI is effective in reversing EIA after 15 min in adolescents and in protecting EIA after 30-60 days in adolescents. Larger studies are needed to assess the effect of FF/VI on EIA.

The Association between IgG and Disease Severity Parameters in CF Patients.

Assessing disease severity in patients with cystic fibrosis (CF) is essential when directing therapies. Serum immunoglobulin G (IgG) levels increase with disease severity. Lung clearance index (LCI) is recognized as an outcome measure for CF clinical trials. Our aim was to evaluate the correlations between IgG and disease severity markers. This was a single-center retrospective study, evaluating association between IgG and markers of severity in CF patients (including clinical characteristics, lung spirometry, LCI, clinical scores and computed tomography (CT) scores) during stable conditions. There were 69 patients, age 20.5 ± 11.6 years. Nineteen (27.5%) patients had elevated IgG. IgG correlated positively with LCI (r = 0.342, p = 0.005). IgG was higher in pancreatic insufficient (PI) and patients with liver disease (1504.3 ± 625.5 vs. 1229 ± 276.1 mg/dL in PI vs. PS, p = 0.023, and 1702.6 ± 720.3 vs. 1256.2 ± 345.5 mg/dL with vs. without liver disease, p = 0.001, respectively). IgG also correlated positively with CRP, CT score, and days with antibiotics in the previous year (r = 0.38, p = 0.003; r = 0.435, p = 0.001; and r = 0.361, p = 0.002, respectively), and negatively with FEV1% and SK score (r = -0.527, p < 0.001 and r = -0.613, p < 0.001, respectively). IgG correlated with clinical parameters, pulmonary functions, and imaging. However, this is still an auxiliary test, complementing other tests, including lung function and imaging tests. Larger multi-center longitudinal studies are warranted.

Understanding the interplay between factors that influence bone mineral density in CF.

BACKGROUND AND OBJECTIVES: Multiple factors affect bone mineral density (BMD) in cystic fibrosis (CF). Our aim was to perform comprehensive analyses of parameters potentially contributing to BMD. METHODS: A prospective single-center study assessing BMD, and correlations with multiple parameters including pancreatic status, lung functions, 6-minute walk test (6MWT), clinical score (modified Shwachman-Kulczycki [SK] score), vitamin D, nutritional intake, hand grip strength (HGS), habitual physical activity (smart watches), and quality of life (SF-36 questionnaire). RESULTS: Forty CF patients, mean age 18.3 ± 8.1 years, forced expiratory volume in 1 second 74.7% ± 17.9% predicted. Fifteen (37.5%) and 11 (27.5%) had osteopenia and osteoporosis, respectively. BMD was similar in pancreatic sufficient (pancreatic sufficient [PS], n = 15) and insufficient (pancreatic insufficient [PI], n = 25); median hip z score -1.5 ((-2.7)-(+0.2)) vs -1.5 ((-3.5)-(+0.7)), P = .79; spine -0.8 ((-2.2)-(+2)) vs -1.2 ((-4.4)-(+1.5)), P = .39 in PS vs PI, respectively. BMD correlated with HGS (r = .72, P < .001 hip; r = .52, P = .001 spine) and fat-free mass index (r = .81, P < .001 hip; r = .63, P < .001 spine). BMD z score correlated weakly with SK score and moderately with SF-36 general health. Data from smart watches, nutrition questionnaires, and 6MWT did not correlate with BMD. In a multivariate model, age and SK score predicted spine z score BMD. CONCLUSIONS: A substantial number of CF patients have low BMD. Similar rates in PS and PI suggest that other factors, such as disease severity, may contribute to low BMD. SK and age, which can easily be obtained even with limited resources, were the best predictors of low BMD. Further larger multicenter studies are warranted to evaluate the contribution of multifactorial etiologies to low BMD in CF.

Comprehensive cardiopulmonary assessment in α mannosidosis.

INTRODUCTION: α Mannosidosis is an extremely rare, progressive, and complex lysosomal storage disease, characterized by mental retardation, hearing impairment, coarse facial features, skeletal abnormalities, and pulmonary involvement. While bone marrow transplantation has been the only therapeutic option to date, nowadays new treatment options are being explored, which may affect pulmonary and exercise capacity. AIM AND METHODS: To assess cardiopulmonary involvement in patients with α mannosidosis by pulmonary function tests, cardiopulmonary exercise testing, and low irradiation chest computed tomography (CT). RESULTS: Five patients aged 11 to 28 years were followed in our Respiratory-Metabolic Clinic. All five had pulmonary symptoms and received inhaled therapy. Three patients underwent bone marrow transplantation. Parenchymal lung disease was evident in 3/5 chest CT tests. Pulmonary function tests were abnormal in all patients and showed obstructive/restrictive impairment with air trapping. All five patients showed reduced peak oxygen uptake (median 23.1; range 20.4-32.2 mL/minute/kg, median %predicted 62; range %predicted 59-79). CONCLUSIONS: Pulmonary involvement is a known complication in this rare disease. Comprehensive cardiopulmonary evaluation is feasible among these patients and may help in assessing disease progression and response to new treatment modalities.

The Effect of a 30-Min Water-Pipe Smoking Session on Cognitive Measures and Cardio-Pulmonary Parameters.

INTRODUCTION: One session of water-pipe tobacco smoking (WPS) can increase carboxyhemoglobin (COHb) to levels comparable to those reported in carbon monoxide poisoning, which may cause memory impairment and confusion. METHODS: A prospective study evaluating healthy volunteers pre- and post-30 min of WPS session. Primary outcome parameters were executive cognitive measures [digit span test and Paced Auditory Serial Addition Test (PASAT)]. The effect of repeated cognitive testing 30 min apart without WPS was evaluated in age- and sex-matched healthy volunteers. Secondary outcome parameters included cardio-pulmonary, COHb, serum nicotine, and cytokine changes. RESULTS: Thirty-five subjects aged 25.6 ± 4.5 years smoked water-pipe for a 30-min session. Control group included 20 subjects aged 25.2 ± 5.1 years. Digit span test median score decreased after WPS (16 and 15, respectively, p = .003), insignificant decrease in controls. Median PASAT score increased after WPS (49 and 52, respectively, p = .009); however, a much larger significant increase was observed in controls (p ≤ .001). One WPS session resulted in significant increases in heart and respiratory rates and significant decrease in FEF25-75%. Post WPS, median COHb levels increased (from 2.2% to 10.7%, p < .0001) as did median serum nicotine levels (from 1.2 to 26.8 ng/mL, p < .0001). Serum cytokines levels: IL-2 and IL-6 increased (p < .0001 for each), and IL-10 and IL-5 decreased (p < .0001 and p = .04, respectively). CONCLUSIONS: One session of WPS resulted in significant negative effects on cognitive executive measures, significant increases in COHb and serum nicotine levels, and significant changes in serum cytokines. Our findings call for increasing awareness towards the possible consequences of cognitive alterations following a 30-min session of WPS. IMPLICATIONS: One 30-min session of water-pipe smoking resulted in negative effects on executive cognitive measures, increased carboxyhemoglobin and serum nicotine, and significant changes in serum cytokine levels. This study adds to the accumulating evidence on the harmful effects of water-pipe smoking, a growing epidemic, and calls for awareness of its possible consequences of acute cognitive alterations.

Six-minute walk, lung clearance index, and QOL in bronchiolitis obliterans and cystic fibrosis.

INTRODUCTION: The 6-min walk test (6MWT) predicts outcome in pulmonary hypertension. Recently, its use was reported in both cystic fibrosis (CF) and bronchiolitis obliterans (BO). While the 6MWT is a simple, non-invasive and inexpensive tool, lung clearance index (LCI) measurement requires expensive equipment and expertise. We aimed to evaluate 6MWT in BO and CF, and to compare to MBW (multiple breath washout), pulmonary function tests and quality of life (QOL). METHODS: A prospective single center study assessing 6MWT, MBW, spirometry, whole-body plethysmography and QOL (SF-36 questionnaire) in BO and CF patients and correlations between them. RESULTS: Thirty-three BO patients and 37 CF patients. LCI was significantly higher in BO (12.4 ± 4.2 vs 10.5 ± 3.4, P = 0.044) while FEF 25-75% was significantly lower in BO (43.9 ± 24.4 vs 60.8 ± 30.8, P = 0.014). 6MWD was 474.8 ± 76.3 in BO and 506.6 ± 70 in CF (P > 0.05). There was no correlation between 6MWD and LCI in these small study groups There were few correlation between spirometry prameters and 6MWD. In CF, SF-36 scores correlated with pulmonary functions. CONCLUSIONS: The 6MWT is an easy-to-perform test that may be helpful in chronic lung diseases in regions with limited resources. However,with the current limited data, 6MWT cannot replace LCI or spirometry as a marker of disease progression. Is is suggested that, together with QOL, the 6MWT may provide a global estimation of the physiological and general well-being of these patients. Further larger multi-center studies are warranted to evaluate the correlations of 6MWT with pulmonary physiology parameters in various chronic diseases.