Lower respiratory tract infection

Overview
While often used as a synonym for pneumonia, the rubric of lower respiratory tract infection can also be applied to other types of infection including lung abscess, acute bronchitis, and emphysema.

Symptoms include shortness of breath, weakness, high fever, coughing and fatigue. Commonly known as the most prolific cause of death amongst all infectious diseases, with 3.9 million people killed in 2002 - accountable for 6.8% of worldwide human deaths for that year.

Lower respiratory tract infections
Lower respiratory tract infections place a considerable strain on the health budget and are generally more serious than upper respiratory infections. Since 1993 there has been a slight reduction in the total number of deaths from lower respiratory tract infection. However in 2002 they were still the leading cause of deaths among all infectious diseases accounting for 3.9 million deaths worldwide and 6.9% of all deaths that year. [1]

There are a number of acute and chronic infections that can affect the lower respiratory tract, the focus of this paper is to look at the two most common infections, Bronchitis and Pneumonia, as identified by the Therapeutic guidelines. [2] Although influenza affects the lower respiratory tract, it also affects the upper respiratory tract (shown in figure 1, [3]) and hence it will not be discussed here. Antibiotics are often thought to be the first line treatment in lower respiratory tract infections however as discussed later these are not indicated in viral infections. It is important to use appropriate antibiotic selection based on the infecting organism and to ensure this therapy changes with the evolving nature of these infections and the emerging resistance to conventional therapies. [4] H influenzae and M catarrhalis are of increasing importance in both community acquired pneumonia (CAP) and acute exacerbation of chronic bronchitis (AECB) while the importance of S pneumoniae is declining. It has also become apparent the importance of atypical pathogens such as C pneumoniae, M pneumoniae and L pneumophila, in CAP. [4]

Bronchitis
Bronchitis can be classified as either acute or chronic. Acute bronchitis can be defined as acute bacterial or viral infection of the larger airways in healthy patients with no history of recurrent disease. [2] It affects over 40 adults per 1000 each year and consists of transient inflammation of the major bronchi and trachea. [6] Most often it is caused by viral infection and hence antibiotic therapy is not indicated in immunocompetent individuals. [7-9] There are no effective therapies for viral bronchitis. [9, 10] Treatment of acute bronchitis with antibiotics is common but controversial as their use has only moderate benefit weighted against potential side effects (nausea and vomiting), increased resistance, and cost of treatment in a self-limiting condition. [6, 11] Beta2 agonists are sometimes used to relieve the cough associated with acute bronchitis. In a recent systematic review it was found there was no evidence to support their use. [9]

AECB are frequently due to non-infective causes along with viral ones. 50% of patients are colonised with Hemophilus Influenzae Streptococcus pneumoniae or Moraxella catarrhalis. [2] Antibiotics have only been shown to be effective if all three of the following symptoms are present:- increased dyspnoea, increased sputum volume and purulence. In these cases 500mg of Amoxycillin orally, 8 hourly for 5 days or or 100mg doxycycline orally bd for 5 days should be used. [8]

Pneumonia
Pneumonia is a serious infection of the small bronchioles and alveoli that can involve the pleura. It occurs in a variety of situations and treatment must vary according to the situation. [10] It is classified as either community or hospital acquired depending on where the patient contracted the infection. It is very life-threatening in the elderly or people with illnesses that affect the immune system (diabetes). [12, 13] The most common treatment is antibiotics and these vary in their adverse effects and their effectiveness. [12] Pneumonia is also the leading cause of death in children less than fives years of age. [14] The most common cause of pneumonia is pneumococcal bacteria, Streptococcus pneumoniae accounts for 2/3 of bacteremic pneumonias. [15] A dangerous type of lung infection with a mortality rate of around 25%. [13] For optimal management of a pneumonia patient the following must be assessed;- pneumonia severity (including where to treat eg. Home, hospital or intensive care), identification of causative organism, analgesia of chest pain, the need for supplemental oxygen, physiotherapy, Hydration, bronchodilators and possible complications of emphysema or lung abscess. [16]

For community acquired respiratory infections the appropriate use of fluoroquinolones is a therapeutic option. These have been demonstrated to have targeted in vitro activity against both the typical and atypical pathogens of interest. [17, 18] The newer fluoroquinolones (eg, moxifloxacin or gatifloxacin) have extended gram +ve activity and once daily dosing and hence are potential first line in the treatment of lower respiratory tract infections. [4] However it is clinical response that is the best indicators of efficacy and moxifloxacin or gatifloxacin have been proven to be effective against community acquired respiratory tract infections clinically. [19, 20]

Antibiotic Choice
With increased development of drug resistance, traditional empirical treatments are becoming less effective, hence it is important to base antibiotic choice on isolated bacteria and sensitivity tests. According to the Cochrane review of antibiotic use in CAP in adults, the current evidence from RCTs is insufficient in order to make evidenced based decisions on the antibiotic of choice. Further studies are required to make these decisions. [12] For children they found amoxicillin or procaine penicillin to have greater effect than co-trimoxazole for the treatment of CAP. In hospital settings, penicillin and gentamycin was found to be more effective than chloramphenicol, with oral amoxicillin giving similar results to injectable penicillins. [14] In another review of children with severe pneumonia oral antibiotics were found to be as effective as injectable ones without the side effects of pain risk of infection and high cost. [21] Also in a Cochrane review azithromycin has been shown to be no better than Amoxycillin or Amoxycillin with clavulanic acid in the treatment of lower respiratory infections. [22] The AMH list Amoxycillin as first line of AECB and community acquired pneumonia where as IV azithromycin is first line if high risk of death. If severe hospital acquired pneumonia it recommends IV gentamicin and ticarcillin with clavulanic acid. [23]

Non-Pharmacological Treatments
The main stay of non pharmacological treatment for many years has been rest and increased fluid intake. Although it is common for doctors and other health professional to recommend extra fluid intake a Cochrane systematic review could find no evidence for or against increased fluid intake. Although the idea of replacing fluids lost through fever and rapid breathing was sound, some observational studies reported harmful effects such as dilution of blood sodium concentration leading to headache, confusion or possibly seizures. [24] Rest will allow the body to conserve energy to fight off the infection. Physiotherapy is indicated in some types of pneumonia and should be encouraged where appropriate. [16]

Complementary Therapies
Chickweed taken orally has been used for many years to reduce fever and phlegm associated with bronchitis. It is believed to act as an expectorant and although the pharmacological actions of several constituents suggest it may be useful, controlled studies are not available to confirm its effectiveness. [25]

A systematic review of Chinese herbs used in the treatment of acute bronchitis found that there was weak evidence for their use, but there was insufficient quality data to recommend them. The benefit found may be due to study design or publication bias. Hence they should be used carefully because their safety is largely unknown. [26]

Thyme is approved by commission E in the treatment of bronchitis and there is encouraging data for its use in chronic bronchitis when used in combination with other herbs, however there is no stand-alone data. [25]

The use of Vitamin C is commonly thought to act to prevent colds and other respiratory infections. However according to a recent Cochrane review the evidence is too weak to support its widespread use as a prophylactic in preventing pneumonia in the general population. It may be reasonable to use in high risk patients with low plasma levels of vitamin C due to its low cost and risk associated with is use. [27] Vitamin A has been successfully used to reduce the mortality and severity of respiratory infection with measles. However in a review of non-measles pneumonia it was not found to have any benefit or harmful effects. [28]

For the treatment of pneumonia baical skullcap was shown to be as effective as piperacillin after one treatment. The piperacillin group resulted in 4 of 30 patients with fungal infections while there where none in the baical skullcap group. [25]

The Future
It is likely that the future treatment of lower respiratory tract infections will consist of new antibiotics aimed at facing the problems associated with the constant emergence of antibiotic resistance. With resistance evolving so rapidly future treatments may include the use of vaccines to prevent these infections. Although a Cochrane systematic review of a polysaccharide pneumococcal vaccine didn’t reduce the pneumonia or there related deaths in adults, but was able to reduce incidence of more specific outcomes such as pneumococcal disease in the elderly. [13] So it is hoped with further developments these will become more effective against pneumonia.

Vaccination of patients with AECB in the autumn months is thought to have a positive effect in reducing the severity and number of exacerbations over winter. The oral vaccine described in this review was able to decrease the carriage or non-typeable Haemophilus influenzae that is a common cause of exacerbations to chronic bronchitis. [29] With good planing and further research these types of vaccines may reduce the burden associated with lower respiratory diseases.

There are few treatments available for viral forms of bronchitis and pneumonia. Respiratory syncytial virus (RSV), the main cause of these in children, could be potentially treated using a new monoclonal antibody (mAb) Motavizumab. In animal trials it reduced antibody titres 100 lower than the only drug currently available to treat the condition. [30] This holds great promise for future treatments of LRTI.