Increased Sputum Production Research Articles

Tobramycin solution for inhalation in cystic fibrosis patients: a review of the literature

Cystic fibrosis patients suffer increased sputum production and a notable decline in respiratory function throughout the progression of their disease. Patients are left vulnerable to respiratory colonization/infection from a number of pathogens, including Pseudomonas aeruginosa. At present, the only antibiotic formulation that is FDA approved for aerosolized delivery is tobramycin solution for inhalation (TSI). TSI allows for targeted antibiotic delivery to the lungs and is indicated for maintenance therapy in cystic fibrosis patients infected with P. aeruginosa. Studies demonstrate that cyclical treatment with TSI is associated with an increase in respiratory function and a decrease in sputum density in cystic fibrosis patients. Additional benefits include fewer hospitalizations and a decreased need for systemic antibiotics. However, because of the need for chronic administration, issues such as emergence of resistant organisms and toxicity are a potential concern and have also been evaluated. This review details the pharmacology of TSI and literature involving its use in cystic fibrosis patients.

Association Between Amount Of Smoking With Chronic Cough And Sputum Production

Background: Smoking is a major cause of respiratory disease. We evaluated the association between the amount of chronic smoking with chronic cough and sputum production as a surrogate of pulmonary abnormalities Methods: 139 patients who underwent left ventricular ejection fraction measurement for clinical reasons, were evaluated for the presence of chronic cough and sputum production with reference to the length and amount of smoking. Results: The length and amount of smoking increased the risk of sputum production (smoking less than 10 pack years (9 of 48 18.8% vs smoking more than 10 pack years 38 of 108, 35.2%, OR: 1.3 CI 1.03-1.5, p=0.03). The length of smoking over 50 pack years vs less than 5 pack years was also significantly associated with chronic cough (24 of 31, 77.4% vs 22 of 52, 42.3%, OR: 4.7 CI: 1.7-12.7, p =0.002). Furthermore the mean length of smoking was significantly longer in patients with chronic cough (34.9  38.2 vs 49.1  40.2, p=0.03) or increased sputum production (34.6 39 vs 56.0  40.4, p=0.002). Conclusion: Increasing in length and amount of smoking is associated with increase risk for chronic cough and sputum production consistent with dose dependent negative effect of chronic smoking.

Failure of levofloxacin treatment in community-acquired pneumococcal pneumonia

BackgroundStreptococcus pneumoniae is the leading cause of community-acquired pneumonia (CAP). High global incidence of macrolide and penicillin resistance has been reported, whereas fluoroquinolone resistance is uncommon. Current guidelines for suspected CAP in patients with co-morbidity factors and recent antibiotic therapy recommend initial empiric therapy using one fluoroquinolone or one macrolide associated to other drugs (amoxicillin, amoxicillin/clavulanate, broad-spectrum cephalosporins). Resistance to fluoroquinolones is determined by efflux mechanisms and/or mutations in the parC and parE genes coding for topoisomerase IV and/or gyrA and gyrB genes coding for DNA gyrase. No clinical cases due to fluoroquinolone-resistant S. pneumoniae strains have been yet reported from Italy.Case presentationA 72-year-old patient with long history of chronic obstructive pulmonary disease and multiple fluoroquinolone treatments for recurrent lower respiratory tract infections developed fever, increased sputum production, and dyspnea. He was treated with oral levofloxacin (500 mg bid). Three days later, because of acute respiratory insufficiency, the patient was hospitalized. Levofloxacin treatment was supplemented with piperacillin/tazobactam. Microbiological tests detected a S. pneumoniae strain intermediate to penicillin (MIC, 1 mg/L) and resistant to macrolides (MIC >256 mg/L) and fluoroquinolones (MIC >32 mg/L). Point mutations were detected in gyrA (Ser81-Phe), parE (Ile460-Val), and parC gene (Ser79-Phe; Lys137-Asn). Complete clinical response followed treatment with piperacillin/tazobactam.ConclusionThis is the first Italian case of community-acquired pneumonia due to a fluoroquinolone-resistant S. pneumoniae isolate where treatment failure of levofloxacin was documented. Molecular analysis showed a group of mutations that have not yet been reported from Italy and has been detected only twice in Europe. Treatment with piperacillin/tazobactam appears an effective means to inhibit fluoroquinolone-resistant strains of S. pneumoniae causing community-acquired pneumonia in seriously ill patients.

The physiological rationale of heat and moisture exchangers in post-laryngectomy pulmonary rehabilitation: a review

Total laryngectomy results in a permanent disconnection of the upper and lower airways and inevitably leads to chronic pulmonary complaints like frequent involuntary coughing, increased sputum production and repeated daily forced expectoration to clean the airway. Heat and moisture exchangers (HMEs), applied in an attempt to compensate for the lost functions of the upper respiratory tract, have been found to diminish these symptoms and improve the quality of life significantly. An HME has three physical properties that might be responsible for these improvements. First, its heat and moisture exchanging capacity improves intra-airway preservation of heat and water. Since the condensation and evaporation of moisture are accompanied by the release and uptake of thermal energy, these parameters are inseparable. Secondly, the HME's resistance may reduce dynamic airway compression, thereby improving ventilation. Thirdly, to some extent, an HME might filter out particles, thereby cleaning inspiratory breathing air. This article summarizes our present knowledge of changes in respiratory physiology after total laryngectomy and the influence of the HME by reviewing the physiological impact of these three physical properties separately for in vitro and in vivo data.

Does ventilator-associated tracheobronchitis need antibiotic treatment?

It is difficult to define ventilator-associated tracheobronchitis (VAT). The most accepted definition includes fever (temperature > 38°C), new or increased sputum production, a microbiologically positive respiratory sample with counts above the accepted thresholds and absence of pulmonary infiltrates on chest X-ray. Although we have no doubt that this pathologic process exists, the main controversy lies on whether this entity has any impact on the outcome and, thus, a specific therapeutic approach is suitable. We will discuss the strengths and drawbacks of the article on this topic published in this issue by Nseir et al.

Pulmonary exacerbations in cystic fibrosis.

The clinical characteristics most relevant to the decision to treat for a pulmonary exacerbation with antibiotics in cystic fibrosis patients were determined. Variables including age, increased cough frequency and sputum production, new crackles and wheezing, asthma, symptomatic sinusitis, hemoptysis, decreased lung function, weight loss, and new acquisition of Pseudomonas aeruginosa were collected in a large prospective multicenter database (Epidemiologic Study of Cystic Fibrosis). During a 12-month baseline period, data from 11692 patients were compared with data collected during the subsequent 6-month study period. Because pulmonary function assessments were unavailable for patients <6 years of age, separate analyses were done for those <6 and >or=6 years of age. The outcome of interest was any antibiotic treatment in the 6-month study period reported as indicated for an exacerbation. Characteristics with the most discriminatory power were determined using stepwise multiple logistic regression. For patients <6 years of age, the strongest independent associations with treatment for a pulmonary exacerbation were new crackles, increased cough frequency, decline in weight, and increased sputum production. For those patients >or=6 years of age, the strongest independent associations were a relative decrease in percent predicted forced expired volume in 1 sec, increased cough frequency, new crackles, and hemoptysis. The presence of three or more of these key characteristics was strongly associated with the occurrence of a treated exacerbation. The reproducibility of the model over time was confirmed by application to a subsequent set of data. This model has potential for use as an outcome measure in clinical trials, and to assist in treatment decisions for individual patients.

Head-down tilt and manual hyperinflation enhance sputum clearance in patients who are intubated and ventilated

The purpose of this prospective randomised cross-over study was to measure peak expiratory flow rates during manual hyperinflation and to determine if the addition of a head-down tilt to physiotherapy treatment increased sputum production in patients who are intubated and ventilated. Twenty patients who were intubated, ventilated and haemodynamically stable were randomised to a sequence of physiotherapy treatment in a flat side-lying or a head-down tilt position. Peak expiratory flow rates were measured for each breath during manual hyperinflation using a Vitalograph peak flow meter. Sputum wet weight was collected for each treatment position and static pulmonary compliance was measured before and immediately following physiotherapy treatment. There was a significant increase in peak expiratory flow (p < 0.001) and sputum production (p = 0.008) in the head-down tilt position. The mean difference and 95% confidence intervals for expiratory flow were 0.17 (0.15 to 0.19) l/sec and for the wet weight of sputum 1.97 (0.84 to 3.10) g. The peak expiratory flow rate was sufficient to produce annular flow in both flat side-lying (1.97 +/- 0.09) l/sec and in the head-down tilt position (2.14 +/- 0.08) l/sec. Static pulmonary compliance improved significantly following physiotherapy treatment (p = 0.003). The mean difference and 95% confidence intervals pre- and post-treatment for static pulmonary compliance were 5.18 (2.14 to 8.22) ml/cmH(2)O. The results suggest that addition of a head-down tilt to physiotherapy treatment, including manual hyperinflation, in patients who are intubated and ventilated, increases sputum production and improves peak expiratory flow.

Acute exacerbations of COPD.

Acute exacerbations of COPD (AECOPD) are a common cause of morbidity and mortality. There is a need for a standardised definition of an exacerbation of COPD. The common aetiological factors are bacterial, viral infection and air pollutants. Exacerbations of COPD may adversely affect the natural history of COPD. Several strategies are available now to prevent or reduce exacerbations of COPD including immunisation against influenza and inhaled corticosteroids in patients with moderate/severe disease. The mainstay of treatment involves increasing bronchodilator therapy, systemic glucocorticoids which have now been shown to have a beneficial effect. The circumstances for the use of antibiotic therapy is now established in patients with increased breathlessness, increased sputum production and/or sputum purulence. In those with respiratory failure, noninvasive ventilation has been shown to reduce intubation rates, shorten lengths of hospitalisation, and improve mortality. Early or immediate supported discharge for selected patients has been shown to be effective in the management of patients with COPD.

Acute exacerbations of COPD.

Acute exacerbations of COPD (AECOPD) are a common cause of morbidity and mortality. There is a need for a standardised definition of an exacerbation of COPD. The common aetiological factors are bacterial, viral infection and air pollutants. Exacerbations of COPD may adversely affect the natural history of COPD. Several strategies are available now to prevent or reduce exacerbations of COPD including immunisation against influenza and inhaled corticosteroids in patients with moderate/severe disease. The mainstay of treatment involves increasing bronchodilator therapy, systemic glucocorticoids which have now been shown to have a beneficial effect. The circumstances for the use of antibiotic therapy is now established in patients with increased breathlessness, increased sputum production and/or sputum purulence. In those with respiratory failure, noninvasive ventilation has been shown to reduce intubation rates, shorten lengths of hospitalisation, and improve mortality. Early or immediate supported discharge for selected patients has been shown to be effective in the management of patients with COPD.

Do Bacteria Cause Exacerbations of COPD?

Exacerbations of COPD, which include combinations of dyspnea, cough, wheezing, increased sputum production (and a change in its color to green or yellow), are common. The role of bacterial infection in causing these episodes and the value of antibiotic therapy for them are debated. An assessment of the microbiological studies indicates that conventional bacterial respiratory pathogens, such as Streptococcus pneumoniae and Haemophilus influenzae, are absent in about 50% of attacks. The frequency of isolating these organisms, which often colonize the bronchi of patients in stable condition, does not seem to increase during exacerbations, and their density typically remains unchanged. Serologic studies generally fail to show rises in antibody titers to H influenzae; the only report available demonstrates none to Haemophilus parainfluenzae; and the sole investigation of S pneumoniae is inconclusive. Trials with vaccines against S pneumoniae and H influenzae show no clear benefit in reducing exacerbations. The histologic findings of bronchial biopsies and cytologic studies of sputum show predominantly increased eosinophils, rather than neutrophils, contrary to what is expected with bacterial infections. The randomized, placebo-controlled trials generally show no benefit for antibiotics, but most have studied few patients. A meta-analysis of these demonstrated no clinically significant advantage to antimicrobial therapy. The largest trials suggest that antibiotics confer no advantage for mild episodes; with more severe attacks, in which patients should receive systemic corticosteroids, the addition of antimicrobial therapy is probably not helpful.

Introduction: the role of bacterial infection in chronic bronchitis.

Acute exacerbations of chronic bronchitis reflect increased airway inflammation and are characterised by one or more symptoms of increased sputum production, sputum purulence, and breathlessness. The causes are multifactorial, and bacterial infection is involved in about half of cases. A proportion of patients also have chronic colonization of the bronchial tree between exacerbations, and this may act as a stimulant of airway inflammation. Colonization represents a balance in which compromised host defences limit bacterial numbers but do not eradicate them. The balance is upset during an exacerbation, often due to extraneous factors such as a viral infection or air pollution, leading to increased bacterial numbers and consequently more inflammation. In patients with severe airway damage, infective exacerbations are more likely to occur, and serious consequences may result if baseline lung function is impaired or there are comorbid conditions. In these circumstances, the exacerbation is less likely to resolve spontaneously. Antibiotic treatment benefits patients by achieving bacterial eradication and resolution of the inflammatory response. However, since superficial mucosal infections may resolve spontaneously, there are serious concerns about widespread antibiotic use in patients with more trivial illness. Future studies should include better definition of the type of patients enrolled, improved techniques to determine bacteriological response, and better outcome measures.

Mucous Cell Metaplasia in the Airways of Rats Exposed to Machining Fluids

Mucous Cell Metaplasia in the Airways of Rats Exposed to Machining Fluids. Gordon, T., and Harkema, J. R. (1995). Fundam. Appl. Toxicol 28, 274-282.Occupational exposure to microbial-contaminated machining fluids is associated with a variety of adverse pulmonary effects including chronic bronchitis and increased sputum production. We have previously demonstrated in F344 rats that inhaled endotoxin can increase the amount of stored intraepithelial mucosubstances (Vs) in the respiratory tract. The purpose of the present study was to examine the effect of endotoxin-contaminated machining fluid aerosols on mucous production. Rats were exposed to aerosols of pyrogen-free water, 1 or 10 mg/m3 used machining fluid, or 10 mg/m3 unused machining fluid for 3 hr/day for 3 days. Twenty-four hours after the final exposure, right lung lobes were lavaged and the nasal cavity and left lung were fixed in formalin. The amount of Alcian blue/periodic acid-Schiff-stained mucosubstances was determined by morphometry. Exposure to 10 mg/m3 used machining fluid (equivalent to 0.8 μg/m3 endotoxin) produced a significant increase in Vs in the epithelial lining of both the nasal septum and intrapulmonary airways. These changes in Vs were accompanied by a significant increase in total cells and neutrophils in the lavage fluid. No changes in stored mucosubstances or lavage parameters were found in animals exposed to 1 mg/m3 used machining fluid aerosols. A significant increase in Vs was observed in the nasal septum but not in the intrapulmonary airways of animals exposed to 10 mg/m3 unused machining fluids (no measurable endotoxin). These results suggest that in addition to endotoxin, nonendotoxin components of machining fluids may contribute to the increase in sputum and chronic bronchitis reported for workers exposed to machining fluid aerosols.

Mucous Cell Metaplasia in the Airways of Rats Exposed to Machining Fluids

Occupational exposure to microbial-contaminated machining fluids is associated with a variety of adverse pulmonary effects including chronic bronchitis and increased sputum production. We have previously demonstrated in F344 rats that inhaled endotoxin can increase the amount of stored intraepithelial mucosubstances (Vs) in the respiratory tract. The purpose of the present study was to examine the effect of endotoxin-contaminated machining fluid aerosols on mucous production. Rats were exposed to aerosols of pyrogen-free water, 1 or 10 mg/m3 used machining fluid, or 10 mg/m3 unused machining fluid for 3 hr/day for 3 days. Twenty-four hours after the final exposure, right lung lobes were lavaged and the nasal cavity and left lung were fixed in formalin. The amount of Alcian blue/periodic acid-Schiff-stained mucosubstances was determined by morphometry. Exposure to 10 mg/m3 used machining fluid (equivalent to 0.8 μg/m3 endotoxin) produced a significant increase in Vs in the epithelial lining of both the nasal septum and intrapulmonary airways. These changes in Vs were accompanied by a significant increase in total cells and neutrophils in the lavage fluid. No changes in stored mucosubstances or lavage parameters were found in animals exposed to 1 mg/m3 used machining fluid aerosols. A significant increase in Vs was observed in the nasal septum but not in the intrapulmonary airways of animals exposed to 10 mg/m3 unused machining fluids (no measurable endotoxin). These results suggest that in addition to endotoxin, nonendotoxin components of machining fluids may contribute to the increase in sputum and chronic bronchitis reported for workers exposed to machining fluid aerosols.

Effect of inhaled endotoxin on intraepithelial mucosubstances in F344 rat nasal and tracheobronchial airways.

Increased sputum production and chronic bronchitis are associated with occupational exposure to endotoxin-contaminated organic ducts. The present study examined whether repeated exposure to occupationally relevant concentrations of airborne endotoxin in the F344 rat can alter the volume density of stored intraepithelial mucosubstances (Vs) in the respiratory tract. Rats were exposed to saline or endotoxin aerosols for 3 h/day for 3 days and were killed 24 h after the last exposure. Quantitative histochemistry of Vs in airway epithelium was examined at three distinct levels of the respiratory tract (nose, trachea, and lung). Exposure to endotoxin produced a dose-dependent increase in Vs in the intrapulmonary airways. The quantity of Vs in the intrapulmonary airways was significantly increased in animals exposed to as little as 0.3 micrograms/m3 endotoxin. Significant increases in Vs were observed in the trachea only after exposure to > or = 3.1 micrograms/m3 endotoxin, whereas no significant changes were observed in the nasal airways even at concentrations as high as 52.4 micrograms/m3. These results are consistent with earlier findings in which repeated instillation of endotoxin produced significant increases in Vs in the epithelial lining of the pulmonary airways and demonstrate that inhaled endotoxin may play a role in the increase in sputum and chronic bronchitis reported for workers exposed to organic dusts.

Pathological Cases of the Month

A 6-YEAR-OLD BOY with cystic fibrosis presented to the hospital with low-grade temperature, cough, increased sputum production, and decreased appetite of 2 weeks' duration. Physical examination revealed a body temperature of 38.5°C, a respiration rate of 25 breaths per minute, a cardiac rate of 130 beats per minute, and a blood pressure of 105/60 mm Hg. The child looked pale and weak. Auscultation of the chest revealed decreased breath sounds and bilateral inspiratory and expiratory rales. Chest roentgenography showed a diffuse bilateral interstitial infiltrate, peribronchial thickening, and moderate hyperinflation. Oxygen saturation, while breathing room air, was 90%. Spirometry results showed a forced expiratory volume of 0.70 (59% of predicted), and a forced expiratory volume to forced vital capacity ratio of 80%. His total leukocyte count was lOXlO 3 mL. Culture of the sputum yielded Pseudomonas aeruginosa and Staphylococcus aureus . The patient was admitted to the hospital for treatment of acute

Antibiotic Therapy for Common Infections

Several important points regarding the treatment of urinary tract infections should be made. Single-dose and short-course antibiotic therapy is appropriate only for women with acute bacterial cystitis due to E. coli. Studies comparing single-dose to full-course therapy have not been sufficiently designed to draw valid statistical conclusions, and only TMP/SMX is recommended at this time. Recurrent UTI in women is almost always due to reinfection, which is best managed by prophylactic antibiotics. Acute bronchitis and acute exacerbations of chronic bronchitis are often due to viral infections, and therefore antibiotic therapy is not always needed. In acute exacerbations of chronic bronchitis, the clearest success rates for antibiotic therapy have been in patients, who have all three of the following symptoms: increased dyspnea, increased sputum production, and sputum purulence. Mupirocin is an important addition to the agents used to treat bacterial skin infections due to streptococcal and staphylococcal strains. In impetigo, mupirocin has been demonstrated to be as effective or superior to oral erythromycin. In prostatitis, data on the fluoroquinolones appears impressive, but further comparative trials are needed. They may become first-line, empiric therapy. The newer oral antibiotics are not recommended as initial, empiric therapy in the outpatient management of common infections, with the possible exception of the treatment of prostatitis. These newer agents may be more important in the treatment of recurrent or resistant infections.

EFFECT OF BARBITAL THERAPY IN THREE CASES OF SEVERE TETANUS

Three patients with severe tetanus were successfully treated by barbital therapy.In the management of tetanus it is important to provide treatment for frequently occurring convulsion or an accumulated convulsive status in addition to antitoxin therapy. The present three patients with severe tetanus showed almost complete suppression of convulsion by administration of thiamylal at a maintenance dose of 4 mg/kg/h. It is necessary, however, to take into account the necessity of using an artificial ventilator, possible occurrence of pulmonary complications accompanied by increased sputum production, heart failure and hypotension. Medication should be discontinued after the dose has been gradually decreased for 2-3 days, when the convulsion has been completely suppressed for 1-2 weeks after initiation of the therapy.

Role of corticosteroids in the development of pneumonia in mechanically ventilated head-trauma victims.

The development of pneumonia was monitored in head-trauma patients requiring mechanical ventilation. Of the 66 patients studied, 15 (23%) developed pneumonia within 14 days after ICU admission. In each case the diagnosis was based on x-ray evidence and at least two of the following: increased white blood cell count, increased fever, and/or increased sputum production with a predominant organism on the sputum stain. Coagulase-positive Staphylococcus aureus was the most common etiologic agent. There was no difference in the occurrence of pneumonia between patients treated with no steroids or with low, moderate, or high steroid doses. Although there was an association between thiopental use and the development of pneumonia, dexamethasone treatment was not a significant risk factor in the development of pneumonia in this patient population.

Circulating Immune Complexes in Patients with Cystic Fibrosis

Circulating immune complexes (CICs) were measured in the sera of clinically stable and acutely infected patients with cystic fibrosis (CF). Twenty CF patients were studied when clinically stable; and additional 18 patients were studied during an acute exacerbation of pulmonary infection as evidenced by fever, tachypnea, increased white blood cell count, increased sputum production, and acute chest x-ray film changes. Three methods for determining CICs were employed: polyethyelene glycol precipitation, a C1q phase assay, and the Raji cell radioimmune assay. Ten of 20 clinically stable CF patients had one or two positive assays for CICs; two of 20 had two positive assays. In contrast, 16 of 18 acutely infected CF patients had a positive CIC test, and 12 of these were positive with two or three of the assays employed. Serum C3 and C4 concentrations and total hemolytic complement activity did not correlate with the presence of CICs in either patient group. These findings suggest that immune complex formation may mediate some of the tissue damage characteristic of CF, although this usually does not involve intravascular complement activation.

Diagnosis and Reversal of Rejection in Experimental and Clinical Lung Allografts

Experience in our patients and dogs with lung transplants has provided reliable criteria for diagnosing rejection and distinguishing it from other pathological processes such as pneumonia and ischemic injury. These criteria include fever; dyspnea; malaise; increased sputum production; decreased arterial oxygen tension; and, most importantly, the rapid development (often within hours) of a roentgenographic alveolar infiltrate without any change in the sputum bacteriology. Using these criteria we have identified multiple rejection episodes in 2 patients and in comparably immunosuppressed dogs. In almost every instance all acute manifestations of rejection, including the roentgenographic infiltrates, have been completely reversed by three to seven large intravenous doses of methylprednisolone given at 12- to 24-hour intervals. In the dogs, reversal of rejection has also been confirmed by gross and microscopical examination of the allograft. These findings show that acute rejection in lung allografts can be reliably identified by noninvasive criteria and successfully reversed.