Dissociation of lung function, dyspnea ratings and pulmonary extension in bronchiectasis

Bronchiectasis is a heterogeneous disease in terms of its clinical and functional presentation. Some isolated parameters have been used to assess the severity of bronchiectasis or its response to treatment. A study was undertaken to evaluate whether lung function, dyspnea and extension of the disease are separate entities in the impact of bronchiectasis upon patients using factor analysis. Patients with bronchiectasis diagnosed by high-resolution computed tomography (HRCT) and airflow obstruction defined by FEV1/FVC<70% were included. Data were collected relating to clinical history, three different clinical ratings of dyspnea (Medical Research Council (MRC), Borg scale and Basal Dyspnea Index), the extent of bronchiectasis and functional variables. A total of 81 patients (mean age (SD): 69.5 (8.7)) years were included. The degree of dyspnea (MRC) was 1.9 (0.8). Mean FEV1 was 1301 ml (56.9% pred.). Four factors were found that accounted for 84.1% of the total data variance. Factor 1 (45.6% of the data variance) included the three measurements of dyspnea. Factor 2 (16% variance) comprised airflow obstruction parameters (FEV1, FEV1/FVC and PEF). Factor 3 (13.8% variance) included RV/TLC and RV (lung hyperinflation). Factor 4 (8.6% variance) included bronchiectasis extent. Dyspnea was more closely correlated with lung hyperinflation (r:0.33-0.54) than with airflow obstruction parameters (r:0.17-0.26). CONCLUSIONS: Airflow obstruction, dyspnea, lung hyperinflation and the lung extent of the bronchiectasis are four independent entities in the impact of bronchiectasis upon patients.     

Lung function abnormalities in different connective tissue diseases

Summary Lung volumes, forced expiratory flow-volume curves, diffusing capacity indexes, and arterial blood gases were measured in 72 non-smoking patients with various connective tissue diseases (13 with rheumatoid arthritis, 17 with systemic lupus erythematosus, 25 with progressive systemic sclerosis, 10 with primary Sjögren's syndrome, 4 with polymyositis, and 3 with mixed connective tissue disease). Small airways disease and a diffusion capacity impairment were the most frequent and marked functional abnormalities in the whole group, and were often present in asymptomatic patients. Different lung function defects seemed to be present in each disease group. In fact, large airway obstruction was prevalent in progressive systemic sclerosis, diffusion capacity impairment in systemic lupus erythematosus, and small airways disease in rheumatoid arthritis. In contrast, primary Sjögren's syndrome appeared to be the connective tissue disease in which lung function abnormalities were less frequent and less pronounced.     

Lung function abnormalities in children with type I diabetes

Recent developments in intrabronchial administration of insulin raise lung function in patients with type I diabetes as important issue. Several studies in adults report abnormalities of lung function of these patients. The aim of this study was to investigate lung function in children with type I diabetes. Twenty-seven children with type I diabetes performed measurement of airway obstruction (forced flow-volume curves), lung volumes and airway resistance (bodyplethysmography) and of pulmonary carbon monoxide diffusion capacity Mean age (+/- SD) of the children was 12.8 +/- 5 years. Mean time between the detection of type I diabetes and the lung function tests was 5.5 years with a variation from I to 17 years.The total airway resistance (Raw) was significantly higher compared to the reference values (P < 0.001). The other lung function parameters were not significantly different from reference values (P > 0.05). In this relatively small study no relationship between lung function abnormalities and age, the duration of disease or level of HbA1c was observed. Our data show that increase of airway resistance do occur in children withtype I diabetes. Progressive abnormalities in lung function might interfere with the promising results of treatment with intrabronchial administration of insulin.     

Airway inflammation in patients with symptoms suggesting asthma but with normal lung function.

The hypothesis that eosinophilic airway inflammation is present in many patients presenting with respiratory symptoms suggestive of asthma but with normal lung function was tested. Thirty-six consecutive patients presenting with these features were studied. Twenty-five asthmatics and 43 healthy volunteers served as control groups. Signs of eosinophilic inflammation in blood and induced sputum were studied. Patients with respiratory symptoms were single-blindly treated with inhaled beclomethasone dipropionate (BDP), 800 microg daily, or placebo for 3 months, and re-examined at 3 months and 1 yr. Patients with respiratory symptoms had higher numbers of blood and sputum eosinophils than healthy persons (p<0.0001), but the degree of eosinophilic inflammation was less pronounced than in asthmatics (p<0.01). Three-month's treatment with BDP significantly reduced total symptom score (p<0.001), cough score (p<0.0001), and the number of blood eosinophils (p<0.01). For cough alone, the improvement was significant compared with placebo (p<0.05). The patients were followed-up for 1 yr, and 17 (55%) still had symptoms but retained normal lung function. Four (13%) patients had developed asthma and another 10 (32%) had become free of symptoms. Using lung function measurements and induced sputum analyses, a group of patients with symptoms suggestive of asthma and signs of eosinophilic airway inflammation but without enough airflow variability to be diagnosed as asthmatics were detected. They seemed to respond favourably to inhaled beclomethasone dipropionate treatment.     

Chronic lung sepsis: lung abscess,bronchiectasis, and empyema

Chronic lung infections including lung abscess, bronchiectasis, and empyema remain serious medical diseases despite the availability of antimicrobial agents. Recent publications contribute to our understanding of disease pathogenesis and management of these entities. The microbial pathogen of lung abscess may be different comparing immunocompetent with immunocompromised patients, supporting a concept for aggressive diagnostic investigations and targeting of specific potential pathogens. The use of surgery in bronchiectasis may be declining, but surgical intervention remains an important strategy with favorable outcomes, especially in cases of focal bronchiectasis. For empyema, maintaining a high index of clinical suspicion may allow for diagnostic thoracentesis in patients with pleural effusions and allow initiation of appropriate tube thoracotomy drainage and use of fibrinolytics. With appropriate management, morbidity and mortality may be limited and outcomes generally favorable.     

Lung structure and function in COPD.

The pathogenesis of chronic obstructive pulmonary disease (COPD) is related to a chronic innate and adaptive inflammatory immune response to inhaled toxic particles and gases, primarily as a result of the tobacco smoking habit. This inflammatory immune process develops in the lungs of everyone that smokes, and there is an association between the extent and severity of this tissue response and the severity of airflow limitation present in the fraction of the smoking population that develops COPD. This infiltration of inflammatory immune cells into the lung tissue is inextricably linked to a tissue repair and remodeling process that enlarges the bronchial mucus glands, thickens the walls and narrows the lumen of conducting airways <2 mm in diameter. A multivariate analysis has shown that thickening of the walls of the small conducting airways and occlusion of their lumen by inflammatory exudates containing mucus explains more of the variance in the association between FEV1 decline and histology in COPD than the infiltration of the tissue by any inflammatory cell type. Emphysematous destruction of the gas exchanging tissue also contributes to the airflow limitation by reducing the elastic recoil pressure available to drive air out of the lung during forced expiration. This tissue destruction begins in the respiratory bronchioles in very close proximity to the small conducting airways that become the major site of obstruction in COPD. The mechanism(s) that allow small airways to thicken in such close proximity to lung tissue undergoing emphysematous destruction remain a puzzle that needs to be solved. As the accumulation of tissue responsible for thickening the small conducting airways is a very different pathological process from the emphysematous destruction of surrounding gas exchanging tissue, we need a better understanding of the pathogenesis of both processes and better methods of separating their relative contribution to airflow limitation in individuals to adequately prevent and treat COPD.     

Lung function abnormalities in HIV‐infected adults and children

Despite the advent of antiretroviral therapy (ART), the human immunodeficiency virus (HIV) epidemic remains a global health crisis with a high burden of respiratory disease among infected persons. While the early complications of the epidemic were dominated by opportunistic infections, improved survival has led to the emergence of non‐infectious conditions that are associated with chronic respiratory symptoms and pulmonary disability. Obstructive ventilatory defects and reduced diffusing capacity are common findings in adults, and the association between HIV and chronic obstructive pulmonary disease is increasingly recognized. There is synergism between viral factors, opportunistic infections, conventional influences like tobacco smoke and biomass fuel exposure, and potentially, the immunological effects of ART on the development of HIV‐associated chronic obstructive lung disease. Pulmonary function data for HIV‐infected infants and children are scarce, but shows that bronchiectasis and obliterative bronchiolitis with severe airflow limitation are major problems, particularly in the developing world. However, studies from these regions are sorely lacking. There is thus a major unmet need to understand the influences of chronic HIV infection on the lung in both adults and children, and to devise strategies to manage and prevent these diseases in HIV‐infected individuals. It is important for clinicians working with HIV‐infected individuals to have an appreciation of their effects on measurements of lung function. This review therefore summarizes the lung function abnormalities described in HIV‐positive adults and children, with an emphasis on obstructive lung disease, and examines potential pathogenic links between HIV and the development of chronic pulmonary disability.     

Immunological abnormalities in bronchiectasis with chronic bronchial suppuration.

Fifty-three patients with bronchiectasis (chronic bronchial suppuration) of unknown cause, in whom the chronic production of purulent sputum was the prominent clinical feature, were investigated for possible immunological abnormalities. They were compared with two control groups comprising 50 patients with chronic bronchitis and emphysema and 33 patients with bronchial asthma. Forty-two patients with bronchiectasis(79%) had at least one abnormality of immunoglobulin, usually elevation of IgA, IgG or IgM. Eight patients had all three immunoglobulin levels raised and this was related to severity of disease. Similar increases in immunoglobulin levels were observed in the control groups, but the frequency and severity of these changes were significantly greater in the bronchiectasis patients. Two patients had IgA deficiency. There was a very high prevalence of rheumatoid factor (52%) and an increased prevalence of antinuclear factor (10%) in the bronchiectasis patients compared with the control groups. The presence of these autoantibodies did not correlate closely with severity of disease. Ten patients with bronchiectasis (19%) had one or more autoimmune disorders, and the association of severe bronchiectasis, Hashimoto's thyroiditis and pernicious anaemia in one patient is described in detail. The immunoglobulin changes, high incidence of autoantibodies and association with autoimmune disorders raises the possibility that in some patients with bronchiectasis (chronic bronchial suppuration) of apparent unknown cause abnormal immune mechanisms may be important in causing or perpetuating the condition.     

Exercise tolerance,lung function abnormalities,anemia, and cardiothoracic ratio in sickle cell patients

Many patients with sickle cell disease (SCD) have a reduced exercise capacity and abnormal lung function. Cardiopulmonary exercise testing (CPET) can identify causes of exercise limitation. Forty‐four consecutive SCD patients (27 HbSS, 11 HbSC, and 6 HbS‐beta thalassemia) with a median age (interquartile range) of 26 (21–41) years underwent pulmonary function tests, CPET, chest x‐ray, and echocardiography to further characterize exercise limitation in SCD. Peak oxygen uptake (V′O₂‐peak), expressing maximum exercise capacity, was decreased in 83% of the studied patients. V′O₂‐peak correlated with hemoglobin levels (R = 0.440, P = 0.005), forced vital capacity (FVC) (R = 0.717, P < 0.0001). Cardiothoracic ratio on chest x‐ray inversely correlated with FVC (R = ?0.637, P < 0.001). According to criteria for exercise limitation, the patients were limited in exercise capacity due to anemia (n = 17), cardiovascular dysfunction (n = 2), musculoskeletal function (n = 10), pulmonary ventilatory abnormalities (n = 1), pulmonary vascular exercise limitation (n = 1), and poor effort (n = 3). In the present study we demonstrate that anemia is the most important determinant of reduced exercise tolerance observed in SCD patients without signs of pulmonary hypertension. We found a strong correlation between various parameters of lung volume and cardiothoracic ratio and we hypothesize that cardiomegaly and relative small chest size may be important causes of the impairment in pulmonary function, that is, reduced long volumes and diffusion capacity, in SCD. Taking into account anthropomorphic differences between SCD patients and controls could help to interpret lung function studies in SCD better. Am. J. Hematol. 89:819–824, 2014. © 2014 Wiley Periodicals, Inc.     

The pattern of lung function abnormalities in cotton textile workers

Reversible airway obstruction has been shown to be a characteristic finding of early byssinosis. In the chronic phase of this disease, the patterns of respiratory abnormalities have not been well defined. We examined the lung function of a cohort of 383 older (45 yr of age or more), active and retired, cotton textile workers seen both in 1973 and in 1979 in Columbia, South Carolina. A group of control subjects consisted of 277 white community residents of comparable age from Lebanon, Connecticut. Using data at follow-up, 25% of the male and 14% of the female cotton textile workers had moderate to severe obstructive airway abnormalities, as opposed to 13 and 5% for male and female control subjects (p less than 0.01). There were fewer persons with restrictive than with obstructive lung patterns among cotton textile workers and control subjects, but again, abnormalities were more prevalent among cotton textile workers. Overall, 50% of male cotton textile workers and 37% of female cotton textile workers had some abnormality of lung function, as opposed to 29% of male and 20% of female control subjects (p less than 0.001). More abnormalities were present in cotton textile workers than in control subjects when only lifetime nonsmokers were examined. We conclude that there is an increased prevalence of both obstructive and restrictive lung function abnormalities among cotton textile workers when compared with control subjects, with the most common pattern being obstructive.     

Factors associated with lung function decline in adult patients with stable non-cystic fibrosis bronchiectasis

BACKGROUND: Bronchiectasis remains a major public health problem, but factors influencing its natural history are not well characterized. The objective of our study was to explore modifiable and nonmodifiable factors associated with lung function decline in a clinical cohort of patients with stable non-cystic fibrosis (CF) bronchiectasis. METHODS: Seventy-six stable adult patients (mean age, 69.9 years; 48.7% men) with bronchiectasis were included. The diagnosis of bronchiectasis was established in all cases by high-resolution CT scanning. Baseline data were collected on clinical history, symptoms, disease extension, treatment, sputum volume, microbiological aspects, laboratory findings, and exacerbations. All patients were invited to attend the clinic every 6 months for 24 months to conduct full spirometry and microbiological analysis of sputum, and to report the number of exacerbations. RESULTS: Overall, the group experienced a rate of decline of lung function (FEV1) of 52.7 mL per year. Independent factors associated with an accelerated decline of lung function were chronic colonization with Pseudomonas aeruginosa (PA) [odds ratio (OR), 30.4; 95% confidence interval (CI), 3.8 to 39.4; p=0.005], more frequent severe exacerbations (OR, 6.9; 95% CI, 2.3 to 10.5; p=0.014), and more systemic inflammation (OR, 3.1; 95% CI, 1.9 to 8.9; p=0.023). Regrettably, none of the long-term treatment strategies evaluated, including the use of long-acting inhaled bronchodilators, inhaled or oral steroids, oxygen therapy, secretion clearance maneuvers, or antibiotics had a significant effect on FEV1 decline. CONCLUSION: Chronic colonization by PA, severe exacerbations, and systemic inflammation are associated with disease progression in non-CF bronchiectasis.     

Nebulised 7% hypertonic saline improves lung function and quality of life in bronchiectasis

Sputum retention is a distressing feature of non-cystic fibrosis bronchiectasis and has been shown to contribute to the vicious cycle of infection seen in this disease. In a previous study we demonstrated that nebulised 7% hypertonic saline was both safe and effective in this patient population. Patients with a clinical diagnosis of non-cystic fibrosis bronchiectasis, confirmed by HRCT, were entered into a randomised single blind cross-over study to evaluate 0.9% sodium chloride (IS) and 7% hypertonic saline (HS). Following a 4 week run in patients received a random order active HS or IS daily for 3 months. A 4 week wash-out phase was included between phases. We report lung function, quality of life, and health care utilisation responses. 32 patients mean age 56.6 years (SD 14.6), 16 male, were recruited of which 28 were randomised and completed the study. Lung function (%change from baseline) improved in HS vs. IS (FEV(1): 15.1, 1.8 p<0.01; FVC: 11.2, 0.7 p<0.01. SGRQ improved significantly from baseline (HS 6.0, IS 1.2; p<0.05). There were reductions in annualised antibiotic usage (HS 2.4, IS 5.4 courses per patient per year), annualised emergency health care utilisation visits were reduced (HS 2.1, IS 4.9 events per patient per year). There were also improvements in sputum viscosity and ease of expectoration (visual analogue scale). Regular use of 7% hypertonic saline improves lung function, quality of life and health care utilisation in non-cystic fibrosis bronchiectasis patients.     

Lung function made easy: assessing lung size

Spirometry is available in most GP surgeries and provides an invaluable tool for assessing respiratory function in chronic obstructive pulmonary disease (COPD) and asthma. Spirometry alone may not provide the clinician with an accurate assessment of lung disease as it misses two important measurements of lung volume. By measuring Residual Volume (RV) and Total Lung Capacity (TLC) it is possible to determine true restrictive or hyperinflated disease processes. Helium dilution, body plethysmography and nitrogen washout are three different methods which may be used to measure lung volume. These tests are normally only provided in the acute setting. Comparing values of RV and TLC to predicted values makes it possible to grade the severity of disease far more accurately than spirometry. Four case studies of asthma, obesity, COPD and pulmonary fibrosis clearly demonstrate anomalies that may arise when interpreting lung disease from spirometry compared to the interpretation made with additional lung volume data.     

Digital clubbing and pulmonary function abnormalities in children with lung disease

Digital clubbing and pulmonary function tests were measured in children, adolescents, and adults with chronic lung diseases to determine pulmonary function correlates with a quantitative measure of clubbing. The group had a mean age of 13.8 +/- 6.0 (SD) years, mean PaO2 of 81 +/- 21 mm Hg, and mean FEV1 of 60% +/- 26% predicted. Digital clubbing was diagnosed in 43 cases when the distal phalangeal depth to interphalangeal depth (DPD/IPD) ratio, measured on a finger cast, was greater than or equal to 1 (greater than 3 SD above mean from 85 controls; no history of pulmonary disease; mean age, 14.8 +/- 7.6). The PaO2 of patients with digital clubbing was 69.4 +/- 2.1 (SEM) mm Hg compared with 88.3 +/- 1.3 mm Hg in those without digital clubbing (P less than 0.0001). Digital clubbing was present in 39 of the 84 (46%) hypoxic patients (PaO2 less than or equal to 88) but only four of the 78 (5%) normoxic patients (P less than 0.0001). The DPD/IPD ratio was negatively correlated with PaO2 in subjects with cystic fibrosis and interstitial fibrosis. Weak negative correlations were seen for all other subjects except asthmatics. Overall, the DPD/IPD ratio was significantly correlated with PaO2 (r = -0.53; P less than 0.0001). The DPD/IPD ratio was correlated with other lung function abnormalities (increased RV, decreased FEV1, and FEF25%-75%) only for the subjects with cystic fibrosis. We conclude that digital clubbing is associated with hypoxemia and airway obstruction. The relation is seen most clearly in subjects with cystic fibrosis, possibly reflecting the prolonged duration of hypoxemia. Digital clubbing is rarely seen in normoxic subjects.     

Penicillin aerosol therapy in bronchiectasis,lung abscess and chronic bronchitis

Modifications in the technic of administering antibiotic aerosols are described. Penicillin blood levels obtained after inhalation are presented. A large amount of unused penicillin remains in the apparatus. Crystalline penicillin is the preparation of choice, since fewer local or systemic reactions have been encountered with its use. Physiological saline appears to be the most satisfactory diluent for penicillin at the present time.Attention is directed towards the importance of a high concentration of penicillin in the sputum, as well as an effective blood level, in therapy of suppurative bronchopulmonary disease. Following penicillin aerosol administration, sputum assays reveal high concentrations of the drug, whereas little or no penicillin is found in the sputum after intramuscular injection.Sputum cultures following courses of therapy with penicillin aerosol show disappearance of penicillin-sensitive grampositive organisms and predominance of gram-negative bacteria, usually of the coli-aerogenes group. Certain sulfonamide aerosols as well as streptomycin may be combined with penicillin in an attempt to eliminate gram-negative as well as grampositive bacteria from sputum cultures.Daily dosage of penicillin aerosol employed in treatment of bronchiectasis, lung abscess and chronic bronchitis varies generally from 150,000 to 500,000 units, although in a few instances 1,000,000 units are recommended.Clinical results of penicillin aerosol therapy in thirty-five patients with bronchiectasis, eight patients with lung abscess and sixteen patients with chronic bronchitis are tabulated, and four case reports with illustrative chest x-rays are presented.Of fifty-nine courses of therapy in thirty-five patients with bronchiectasis, there was marked improvement in fifteen, moderate in twenty-two, slight in fourteen and none in eight. Of seven courses of therapy in five patients with acute lung abscess, marked improvement occurred in four, slight in two and no improvement in one. Of four courses of therapy in three patients with chronic lung abscess, two resulted in marked improvement, one in slight improvement and one showed no change. Of twenty-four courses of therapy in sixteen patients with chronic bronchitis, improvement was marked in twelve, moderate in eight, slight in one and absent in three.Although a final appraisal of the benefit which may be expected from antibiotic aerosol therapy cannot be made at the present time, it is our conclusion that penicillin aerosol therapy constitutes an effective and practical technic which may be added to other forms of therapy in the management of patients with bronchopulmonary suppuration.The crystalline penicillin was supplied by Commercial Solvents Corporation, the sulfacetimide by Schering Corporation, and the oxygen by the Linde Air Products Company. The nebulizers employed in the investigation were supplied by the Vaponefrin Company. An additional fund was contributed by Mr. Cornelius Crane.