Successfully treated but not fit for purpose: paying attention to chronic lung impairment after TB treatment.

In 2013, 86% of patients with newly diagnosed tuberculosis (TB) successfully completed treatment and were discharged from care. However, long-term studies in industrialised and resource-poor countries all point to a higher risk of death in TB survivors than in the general population. The likely explanation is chronic restrictive and obstructive lung disease consequent to TB. We call for better linkages between TB control programmes and respiratory medicine services, a better understanding of the burden of respiratory disability at the end of anti-tuberculosis treatment, and political, programmatic, clinical and research action to improve the quality of life of affected patients.

Timing Matters: Circadian Rhythm in Sepsis, Obstructive Lung Disease, Obstructive Sleep Apnea, and Cancer.

Physiological and cellular functions operate in a 24-hour cyclical pattern orchestrated by an endogenous process known as the circadian rhythm. Circadian rhythms represent intrinsic oscillations of biological functions that allow for adaptation to cyclic environmental changes. Key clock genes that affect the persistence and periodicity of circadian rhythms include BMAL1/CLOCK, Period 1, Period 2, and Cryptochrome. Remarkable progress has been made in our understanding of circadian rhythms and their role in common medical conditions. A critical review of the literature supports the association between circadian misalignment and adverse health consequences in sepsis, obstructive lung disease, obstructive sleep apnea, and malignancy. Circadian misalignment plays an important role in these disease processes and can affect disease severity, treatment response, and survivorship. Normal inflammatory response to acute infections, airway resistance, upper airway collapsibility, and mitosis regulation follows a robust circadian pattern. Disruption of normal circadian rhythm at the molecular level affects severity of inflammation in sepsis, contributes to inflammatory responses in obstructive lung diseases, affects apnea length in obstructive sleep apnea, and increases risk for cancer. Chronotherapy is an underused practice of delivering therapy at optimal times to maximize efficacy and minimize toxicity. This approach has been shown to be advantageous in asthma and cancer management. In asthma, appropriate timing of medication administration improves treatment effectiveness. Properly timed chemotherapy may reduce treatment toxicities and maximize efficacy. Future research should focus on circadian rhythm disorders, role of circadian rhythm in other diseases, and modalities to restore and prevent circadian disruption.

[Chest physical therapy of the distal lung. Mechanical basis of a new paradigm]. / La kinésithérapie respiratoire du poumon profond. Bases mécaniques d'un nouveau paradigme.

Recent medical literature has shown that there has been renewed interest focused on the small airways deep in the lung tissue. Although there is involvement of the distal airways at an early stage in mucus secreting lung diseases, no specific chest physical therapy (CPT) manoeuver has been proposed for small airways clearance. A four-tier classification of CPT has been established with identification of its benefits at each level of a monoalveolar respiratory tract model. The usual expiratory techniques directed towards the upper and middle respiratory tract are not applicable to the small airways and new paradigm is proposed appropriate to their specific mechanical characteristics. This comprises a slow resistive inspiratory manoeuver in the lateral position. Clinical auscultation of the lung is the cornerstone of the validation and follow-up of the technique.

Benefits of neuromuscular electrical stimulation prior to endurance training in patients with cystic fibrosis and severe pulmonary dysfunction.

BACKGROUND: We investigated the effect of neuromuscular electrical stimulation (NMES) training prior to endurance training in patients with cystic fibrosis (CF) and severe pulmonary obstruction. METHODS: Fourteen patients with CF (FEV(1) = 35% ± 11% predicted) were prospectively randomized to either a 6-week NMES training program (n = 7) or a 6-week control period (n = 7) both followed by ergocycle (ERGO) training (8 weeks) (NMES + ERGO and control + ERGO groups). Measurements were pulmonary function, mid-thigh circumference, quadriceps strength, 6-min walk distance, maximal exercise capacity on a cycloergometer, plasma biomarkers, insulin resistance (homeostasis model assessment indexes), and quality of life (CF questionnaire for adults and teenagers > 14 years of age [CFQ14 + ], Baseline Dyspnea Index-Transition Dyspnea Index). RESULTS: NMES + ERGO training greatly improved mid-thigh circumference ( + 2.6 ± 0.9 cm vs - 0.4 ± 1.4 cm), quadriceps strength ( + 6 ± 5 kg vs - 2 ± 2 kg), and BMI ( + 0.6 ± 0.6 kg/m(2) vs - 0.5 ± 0.7 kg/m(2) ) compared with control + ERGO training ( P < .05). No differences between groups were found in exercise-induced changes in 6-min walk distance and maximal exercise capacity. However, dyspnea after the 6-minute walk test, the fasting glucose/insulin ratio (calculated as an index of insulin resistance), and physical function and health perception domains of the CFQ14 + improved after NMES + ERGO training compared with control + ERGO training ( P < .05). Significant correlations were found between changes in mid-thigh circumference and muscle strength, ventilation requirements during exercise, insulin sensibility, and the physical function section of CFQ14 + ( P < .05). CONCLUSIONS: NMES training performed prior to endurance training is useful for strengthening peripheral muscles, which in turn may augment gains in body weight and quality of life, further reductions in ventilation requirements during exercise, and retard insulin resistance in patients with CF with severe pulmonary obstruction.

Cigarette smoking, cadmium exposure, and zinc intake on obstructive lung disorder.

BACKGROUND AND OBJECTIVE: This study examined whether zinc intake was associated with lower risk of smoking-induced obstructive lung disorder through interplay with cadmium, one of major toxicants in cigarette smoke. METHODS: Data were obtained from a sample of 6,726 subjects aged 40+ from the Third National Health and Nutrition Examination Survey. The forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were measured using spirometry. Gender-, ethnicity-, and age-specific equations were used to calculate the lower limit of normal (LLN) to define obstructive lung disorder as: observed FEV1/FVC ratio and FEV1 below respective LLN. Zinc intake was assessed by questionnaire. Logistic regression analysis was applied to investigate the associations of interest. RESULTS: The analyses showed that an increased prevalence of obstructive lung disorder was observed among individuals with low zinc intake regardless of smoking status. The adjusted odds of lung disorder are approximately 1.9 times greater for subjects in the lowest zinc-intake tertile than those in the highest tertile (odds ratio = 1.89, 95% confidence interval = 1.22-2.93). The effect of smoking on lung function decreased considerably after adjusting for urinary cadmium. Protective association between the zinc-to-cadmium ratio (log-transformed) and respiratory risk suggests that zinc may play a role in smoking-associated lung disorder by modifying the influence of cadmium. CONCLUSIONS: While zinc intake is associated with lower risk of obstructive lung disorder, the role of smoking cession and/or prevention are likely to be more important given their far greater effect on respiratory risk. Future research is warranted to explore the mechanisms by which zinc could modify smoking-associated lung disease.

Forced expiratory technique, directed cough, and autogenic drainage.

In health, secretions produced in the respiratory tract are cleared by mucociliary transport, cephalad airflow bias, and cough. In disease, increased secretion viscosity and volume, dyskinesia of the cilia, and ineffective cough combine to reduce secretion clearance, leading to increased risk of infection. In obstructive lung disease these conditions are further complicated by early collapse of airways, due to airway compression, which traps both gas and secretions. Techniques have been developed to optimize expiratory flow and promote airway clearance. Directed cough, forced expiratory technique, active cycle of breathing, and autogenic drainage are all more effective than placebo and comparable in therapeutic effects to postural drainage; they require no special equipment or care-provider assistance for routine use. Researchers have suggested that standard chest physical therapy with active cycle of breathing and forced expiratory technique is more effective than chest physical therapy alone. Evidence-based reviews have suggested that, though successful adoption of techniques such as autogenic drainage may require greater control and training, patients with long-term secretion management problems should be taught as many of these techniques as they can master for adoption in their therapeutic routines.

[Effect of inspiratory muscle training on muscle strength and quality of life in patients with chronic airflow limitation: a randomized controlled trial]. / Efecto del entrenamiento muscular inspiratorio sobre la fuerza muscular y la calidad de vida en pacientes con limitación crónica del flujo aéreo. Ensayo clínico aleatorizado.

OBJECTIVE: Chronic airflow limitation (CAL) is a significant cause of illness and death. Inspiratory muscle training has been described as a technique for managing CAL. The aim of the present study was to evaluate the effectiveness of inspiratory muscle training on improving physiological and functional variables. PATIENTS AND METHODS: Randomized controlled trial in which 35 patients with CAL were assigned to receive either an experimental (n=17) or control (n=18) intervention. The experimental intervention consisted of 2 months of inspiratory muscle training using a device that administered a resistive load of 40% of maximal static inspiratory mouth pressure (PImax). Inspiratory muscle strength, exercise tolerance, respiratory function, and quality of life were assessed. RESULTS: Significant improvement in inspiratory muscle strength was observed in the experimental training group (P=.02). All patients improved over time in both groups (P<.001). PImax increased by 8.9 cm H2O per month of training. Likewise, the health-related quality of life scores improved by 0.56 points. CONCLUSION: Use of a threshold loading device is effective for strengthening inspiratory muscles as measured by PImax after the first month of training in patients with CAL. The long-term effectiveness of such training and its impact on quality of life should be studied in a larger number of patients.

Efecto del entrenamiento muscular inspiratorio sobre la fuerza muscular y la calidad de vida en pacientes con limitación crónica del flujo aéreo. Ensayo clínico aleatorizado / Effect of inspiratory muscle training on muscle strength and quality of life in patients with chronic airflow limitation: a randomized controlled trial

Objetivo: La limitación crónica del flujo aéreo (LCFA) es causa importante de morbimortalidad. Para su manejo se describe la rehabilitación pulmonar, que incluye el entrenamiento muscular inspiratorio. El objetivo del presente estudio fue evaluar la efectividad del entrenamiento muscular inspiratorio par mejorar variables fisiológicas y funcionales. Pacientes y métodos: Ensayo clínico controlado y aleatorizado en 35 pacientes con LCFA, de los que 17 recibieron una intervención experimental y 18 una de control. La intervención experimental consistió en un programa de 2 meses de entrenamiento de músculos inspiratorios usando un dispositivo que administraba una resistencia de un 40% de la presión inspiratoria máxima. Se evaluaron la fuerza muscular inspiratoria, la tolerancia al ejercicio, la función respiratoria y la calidad de vida. Resultados: El tratamiento experimental mostró una mejoría significativa en la fuerza muscular inspiratoria (p = 0,02). Todos los pacientes mejoraron a lo largo del tiempo independientemente del tratamiento experimental (p < 0,001); la presión inspiratoria máxima aumentó en 8,9 cmH2O por mes de entrenamiento; asimismo, hubo un aumento de 0,56 puntos en el cuestionario que evaluó la calidad de vida relacionada con la salud. Conclusión: La utilización específica de un dispositivo de carga umbral es efectiva en el fortalecimiento muscular inspiratorio, medido a través de la presión inspiratoria máxima, al primer mes de entrenamiento en pacientes con LCFA. Es necesario estudiar su efecto a largo plazo y su impacto sobre la calidad de vida en un mayor número de pacientes

Objective: Chronic airflow limitation (CAL) is a significant cause of illness and death. Inspiratory muscle training has been described as a technique for managing CAL. The aim of the present study was to evaluate the effectiveness of inspiratory muscle training on improving physiological and functional variables. Patients and methods: Randomized controlled trial in which 35 patients with CAL were assigned to receive either an experimental (n=17) or control (n=18) intervention. The experimental intervention consisted of 2 months of inspiratory muscle training using a device that administered a resistive load of 40% of maximal static inspiratory mouth pressure (PImax). Inspiratory muscle strength, exercise tolerance, respiratory function, and quality of life were assessed. Results: Significant improvement in inspiratory muscle strength was observed in the experimental training group (P=.02). All patients improved over time in both groups (P<.001). PImax increased by 8.9 cm H2O per month of training. Likewise, the health-related quality of life scores improved by 0.56 points. Conclusion: Use of a threshold loading device is effective for strengthening inspiratory muscles as measured by PImax after the first month of training in patients with CAL. The long-term effectiveness of such training and its impact on quality of life should be studied in a larger number of patients

Antioxidant and inflammatory responses of healthy horses and horses affected by recurrent airway obstruction to inhaled ozone.

REASONS FOR PERFORMING STUDY: Inhaled ozone can induce oxidative injury and airway inflammation. Horses affected by recurrent airway obstruction (RAO) have a decreased pulmonary antioxidant capacity, which may render them more susceptible to oxidative challenge. It is currently unknown whether RAO-affected horses are more susceptible to oxidative stress than those unaffected by RAO. OBJECTIVES: To determine whether ozone exposure induces greater oxidative stress and airway inflammation in RAO-affected horses in remission than in healthy horses. METHODS: Seven healthy control horses and 7 RAO-affected horses were exposed to 0.8 ppm ozone for 2 h at rest. RESULTS: At baseline, bronchoalveolar lavage fluid (BALF) ascorbic acid concentrations were lower in RAO-affected horses than healthy controls. Ozone appeared to preferentially oxidise glutathione rather than ascorbic acid 6 h after exposure. Individual healthy and RAO-affected horses demonstrated oxidation of BALF glutathione after ozone exposure. Overall, RAO-affected horses did not demonstrate increased oxidative stress following ozone exposure, compared with healthy horses. Ozone did not induce significant airway inflammation in either group. CONCLUSIONS: RAO-affected horses in remission are not more sensitive to ozone despite a decreased pulmonary antioxidant capacity. Sensitivity to ozone appears to be independent of initial pulmonary antioxidant status. POTENTIAL RELEVANCE: Horses with high susceptibility to oxidative stress may benefit from antioxidant supplementation.

Respiratory findings in pharmaceutical workers.

BACKGROUND: Pharmaceutical workers may be at risk for the development of respiratory problems as a result of their work environment. METHODS: This study investigated 163 female and 35 male workers, employed in a pharmaceutical plant processing different types of medication, primarily antibiotics, in order to characterize the risk of this environment. Chronic respiratory symptoms were recorded by using the British Medical Research Council questionnaire. Acute symptoms, which developed during the work shift, were also recorded. Ventilatory capacity was measured by recording maximum expiratory flow-volume (MEFV) curves on which FVC, FEV1, FEF50, and FEF25 were measured. Controls (113) were selected from a food packing facility. RESULTS: A significantly higher prevalence of chronic respiratory symptoms was recorded among workers (compared to controls), the highest being for sinusitis, nasal catarrh, and dyspnea. There was also a high prevalence of acute symptoms recorded during the workshift. Odds ratio showed that the most significant risk factors for these respiratory findings were smoking and length of time worked in the pharmaceutical industry, particularly in men. Pulmonary function testing demonstrated significantly decreased measured values in comparison to predicted European pulmonary function measurements (P < 0.01). This was particularly pronounced for FEF50 and FEF25, suggesting obstructive changes in smaller airways. CONCLUSIONS: Our data suggest that workers employed in the pharmaceutical industry may develop respiratory symptoms accompanied by ventilatory impairment.

La respiración con los labios fruncidos / Pursed lips breathing

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Pulmonary epithelial lining fluid and plasma ascorbic acid concentrations in horses affected by recurrent airway obstruction.

OBJECTIVE: To determine the pulmonary epithelial lining fluid (ELF) concentrations and degree of oxidation of ascorbic acid in horses affected by recurrent airway obstruction (RAO) in the presence and absence of neutrophilic airway inflammation. ANIMALS: 6 RAO-affected horses and 8 healthy control horses. PROCEDURE: Nonenzymatic antioxidant concentrations were determined in RBC, plasma, and ELF samples of control horses and RAO-affected horses in the presence and absence of airway inflammation. RESULTS: ELF ascorbic acid concentration was decreased in RAO-affected horses with airway inflammation (median, 0.06 mmol/L; 25th and 75th percentiles, 0.0 and 0.4 mmol/L), compared with RAO-affected horses without airway inflammation (1.0 mmol/L; 0.7 and 1.5 mmol/L) and control horses (2.2 mmol/L; 1.4 and 2.2 mmol/L). Epithelial lining fluid ascorbic acid remained significantly lower in RAO-affected horses without airway inflammation than in control horses. Moreover, the ELF ascorbic acid redox ratio (ie, ratio of the concentrations of dehydroascorbate to total ascorbic acid) was higher in RAO-affected horses with airway inflammation (median, 0.85; 25th and 75th percentiles, 0.25 and 1.00), compared with RAO-affected horses without airway inflammation (0.04; 0.02 and 0.22). The number of neutrophils in bronchoalveolar lavage fluid was inversely related to the ELF ascorbic acid concentration (r = -0.81) and positively correlated with the ascorbic acid redox ratio (r = 0.65). CONCLUSIONS AND CLINICAL RELEVANCE: Neutrophilic inflammation in horses affected by RAO is associated with a reduction in the ELF ascorbic acid pool. Nutritional supplementation with ascorbic acid derivatives in horses affected by RAO is an area for further investigation.

[The effects of pulmonary rehabilitation in elderly patients].

Pulmonary rehabilitation is one of the most important treatment modalities for patients with chronic lung disease. To determine the effects of an outpatient pulmonary rehabilitation program for the older members (aged 77 +/- 3 years; seniors) of an elderly patient group with chronic lung disease, we prospectively compared the degrees of improvement of lung function, dyspnea, daily activities and exercise tolerance (6-minute walking distance) after a 9-week rehabilitation program in 27 seniors with chronic lung disease (COPD 18, post-tuberculosis lung disorders 8, lung fibrosis 1; %FEV1 50.9 +/- 17.1%) with that in disease- and %FEV1-matched younger members (aged 70 +/- 2 years; juniors; %FEV1 49.3 +/- 16.1%) of the elderly patient group. All patients performed supervised weekly outpatient exercise and education activities for 9 weeks and a home exercise regimen. Assessments were made before and after the program. Twenty-three of the seniors and 25 of the juniors completed the program. There was no significant difference in the withdrawal rates between these groups. Although lung function and blood gas data had not changed significantly after rehabilitation, the clinical symptoms and the 6-minute walking exercise improved significantly in both groups (Baseline Dyspnea Index focal score: +1.3 +/- 0.9 in the seniors and +0.6 +/- 0.9 in the juniors: 6-minute walking distance: +/- 52 m and +/- 62 m, respectively) and the improvement of the Baseline Dyspnea Index focal score was significantly greater in the seniors than in the juniors. We observed the patients after they had followed the program for 2,000 days and found that the continuation ratio of rehabilitation in the seniors was far inferior to that in the juniors (continuation ratios for 1.2 and 3 years in the seniors were 50.5, 18.0 and 0%, respectively, and in the juniors, 79.5, 66.2 and 61.5%). We concluded that, although the senior elderly patients could benefit from the pulmonary rehabilitation program, it is difficult to maintain this benefit for many years.

Inspiratory muscle strength in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease is associated with a functional weakness of the inspiratory muscles. Multiple factors contribute to the decline in functional strength including hyperinflation of the chest, deterioration in nutritional status, and the indirect effects of an exacerbation. The decreased inspiratory muscle strength contributes to sensations of dyspnea and places individuals at risk for respiratory muscle fatigue. The worsening dyspnea causes individuals to reduce their physical activities and ultimately become physically deconditioned. Maximal inspiratory pressure is commonly used to measure functional strength of the inspiratory muscles, and interventions to minimize the extent of decline include inspiratory muscle training, aerobic exercise training, nutritional supplementation, and methods to prevent exacerbations. In the critical care unit, multiple comorbid conditions contribute to further decline in inspiratory muscle strength, making it important to assess respiratory muscle function regularly.

Inspiratory muscle training in patients with COPD: effect on dyspnea, exercise performance, and quality of life.

OBJECTIVE: The aim of the study was to assess the effect of target-flow inspiratory muscle training (IMT) on respiratory muscle function, exercise performance, dyspnea, and health-related quality of life (HRQL) in patients with COPD. PATIENTS AND METHODS: Twenty patients with severe COPD were randomly assigned to a training group (group T) or to a control group (group C) following a double-blind procedure. Patients in group T (n = 10) trained with 60 to 70% maximal sustained inspiratory pressure (SIPmax) as a training load, and those in group C (n = 10) received no training. Group T trained at home for 30 min daily, 6 days a week for 6 months. MEASUREMENTS: The measurements performed included spirometry, SIPmax, inspiratory muscle strength, and exercise capacity, which included maximal oxygen uptake (VO(2)), and minute ventilation (VE). Exercise performance was evaluated by the distance walked in the shuttle walking test (SWT). Changes in dyspnea and HRQL also were measured. RESULTS: Results showed significant increases in SIPmax, maximal inspiratory pressure, and SWT only in group T (p < 0.003, p < 0.003, and p < 0.001, respectively), with significant differences after 6 months between the two groups (p < 0.003, p < 0.003, and p < 0.05, respectively). The levels of VO(2) and VE did not change in either group. The values for transitional dyspnea index and HRQL improved in group T at 6 months in comparison with group C (p < 0.003 and p < 0.003, respectively). CONCLUSIONS: We conclude that targeted IMT relieves dyspnea, increases the capacity to walk, and improves HRQL in COPD patients.

High-intensity inspiratory muscle training in patients with chronic obstructive pulmonary disease and severely reduced function.

PURPOSE: This study examined the effects of inspiratory muscle training (IMT) with high-intensity inspiratory pressure loads on respiratory muscle performance and exertional dyspnea. METHODS: This was a randomized single-blind clinical trial. Twenty-seven patients with chronic obstructive pulmonary disease (18 men, 9 women) with severe to very severe airflow obstruction and severely limited functional performance were assigned randomly to an IMT group (n = 12) or an educational control group (n = 15). The IMT group trained with a threshold loaded device for 30 minutes a day for 16 weeks using interval training techniques. Training was initiated with inspiratory pressure loads equal to 30% of maximal inspiratory pressure (Plmax) and increased as tolerated to 60% of Plmax. Dependent variables were measured before and after 4 months of IMT: inspiratory muscle strength (Plmax), respiratory muscle endurance (discontinuous incremental threshold loading test [DC-ITL]), dyspnea (Chronic Respiratory Disease Questionnaire [CRQ]), and the Borg Category-Ratio Scale ratings of perceived breathing difficulty (RPBD) at equal loads during the DC-ITL. RESULTS: In the IMT group, Plmax increased from 64 +/- 15 to 75 +/- 17 cm H2O (P < .05), performance on the DC-ITL test increased from a maximal load of 37 +/- 12 to 53 +/- 13 cm H2O (P < .05), RPBD decreased from 5.5 +/- 2.5 to 3.8 +/- 2.6 for equal loads on the DC-ITL (P < .05) and the CRQ Dyspnea Scale improved from 18.1 +/- 5.1 to 22.4 +/- 5.2 (P < .05). CONCLUSIONS: Inspiratory muscle training at high-intensity loads significantly improved inspiratory muscle strength, respiratory muscle endurance, and respiratory symptoms during daily activities and respiratory exertion.

Acute effects of different nutritional supplements on symptoms and functional capacity in patients with chronic obstructive pulmonary disease.

BACKGROUND: Use of nutritional supplements in depleted patients with chronic obstructive pulmonary disease (COPD) requires optimization between positive effects on outcome and potential acute adverse effects on metabolism and exercise performance. OBJECTIVE: The aim of this study was to investigate the acute effects of nutritional supplements on metabolism and exercise capacity in stable COPD patients. DESIGN: In part 1, the effects of 3 different energy loads (placebo, 1046 kJ, and 2092 kJ) with a normal distribution of macronutrients were investigated in 14 COPD patients. In part 2, the effects of a fat-rich compared with a carbohydrate-rich supplement (both 1046 kJ) were studied in 11 COPD patients. The study was performed in a randomized, double-blind, crossover fashion. Metabolic and ventilatory variables were measured postprandially and during a submaximal cycle endurance exercise test. RESULTS: Overall, no immediate negative effects of the supplements were found in part 1. A slight but significant postprandial increase in respiratory quotient was found after the 1046-kJ and 2092-kJ supplements compared with placebo. There was no significant difference in metabolism or exercise capacity after a fat-rich or carbohydrate-rich supplement. Surprisingly, the change in shortness of breath (postprandial compared with preprandial) was significantly greater after the fat-rich supplement. CONCLUSIONS: An energy load up to 2092 kJ had no adverse immediate effect in COPD patients compared with placebo. The subjects who consumed the fat-rich supplement experienced more shortness of breath than did the subjects who consumed the carbohydrate-rich supplement.